Pyrazolobenzamides and derivatives as factor Xa inhibitors

ABSTRACT

The present application describes pyrazolobenzamides and derivatives thereof of Formula I: 
 
P 4 -P-M-M 4   I 
or pharmaceutically acceptable salt forms thereof. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application claims the priority benefit of U.S. ProvisionalApplication No. 60/622,236, filed Oct. 26, 2004, which is expresslyincorporated fully herein by reference

FIELD OF THE INVENTION

This invention relates generally to pyrazolobenzamides and derivativesthereof which are inhibitors of trypsin-like serine protease enzymes,especially factor Xa, pharmaceutical compositions containing the same,and methods of using the same as anticoagulant agents for treatment ofthromboembolic disorders.

BACKGROUND OF THE INVENTION

Activated factor Xa, whose major practical role is the generation ofthrombin by the limited proteolysis of prothrombin, holds a centralposition that links the intrinsic and extrinsic activation mechanisms inthe final common pathway of blood coagulation. The generation ofthrombin, the final serine protease in the pathway to generate a fibrinclot, from its precursor is amplified by formation of prothrombinasecomplex (factor Xa, factor V, Ca²⁺ and phospholipid). Since it iscalculated that one molecule of factor Xa can generate 138 molecules ofthrombin (Elodi, S., Varadi, K.: Optimization of conditions for thecatalytic effect of the factor IXa-factor VIII Complex: Probable role ofthe complex in the amplification of blood coagulation. Thromb. Res.1979, 15, 617-629), inhibition of factor Xa may be more efficient thaninactivation of thrombin in interrupting the blood coagulation system.

Therefore, efficacious and specific inhibitors of factor Xa are neededas potentially valuable therapeutic agents for the treatment ofthromboembolic disorders. It is thus desirable to discover new factor Xainhibitors. In addition, it is also desirable to find new compounds withimproved pharmacological characteristics compared with known factor Xainhibitors. For example, it is preferred to find new compounds withimproved factor Xa inhibitory activity and selectivity for factor Xaversus other serine proteases (i.e., trypsin). It is also desirable andpreferable to find compounds with advantageous and improvedcharacteristics in one or more of the following categories, but are notlimited to: (a) pharmaceutical properties; (b) dosage requirements; (c)factors which decrease blood concentration peak-to-troughcharacteristics; (d) factors that increase the concentration of activedrug at the receptor; (e) factors that decrease the liability forclinical drug-drug interactions; (f) factors that decrease the potentialfor adverse side-effects; and (g) factors that improve manufacturingcosts or feasibility.

SUMMARY OF THE INVENTION

Accordingly, the present invention provides novel pyrazolobenzamides andderivatives thereof that are useful as factor Xa inhibitors orpharmaceutically acceptable salts, solvates, or prodrugs thereof.

The present invention also provides processes and intermediates formaking the compounds of the present invention or a stereoisomer or apharmaceutically acceptable salt, solvate, or prodrug form thereof.

The present invention provides pharmaceutical compositions comprising apharmaceutically acceptable carrier and a therapeutically effectiveamount of at least one of the compounds of the present invention or apharmaceutically acceptable salt, solvate, or prodrug form thereof.

The present invention provides a method for treating thromboembolicdisorders comprising administering to a mammal in need of such treatmenta therapeutically effective amount of at least one of the compounds ofthe present invention or a pharmaceutically acceptable salt, solvate, orprodrug form thereof.

The present invention provides a novel method of treating a patient inneed of thromboembolic disorder treatment, comprising: administering acompound of the present invention or a pharmaceutically acceptable salt,solvate, or prodrug form thereof in an amount effective to treat athromboembolic disorder.

The present invention provides a novel method, comprising: administeringa compound of the present invention or a pharmaceutically acceptablesalt, solvate, or prodrug form thereof in an amount effective to treat athromboembolic disorder.

The present invention provides novel lactam-containing compounds andderivatives thereof for use in therapy.

The present invention provides the use of novel lactam-containingcompounds for the manufacture of a medicament for the treatment of athromboembolic disorder.

These and other objects, which will become apparent during the followingdetailed description, have been achieved by the inventors' discoverythat pyrazolobenzamide compounds of Formula I:P₄-P-M-M₄  I

wherein P, P₄, M, and M₄ are defined below, or pharmaceuticallyacceptable salt or prodrug forms thereof, are effective factor Xainhibitors.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

In a first embodiment, the present invention provides a novel compoundof Formula I:P₄-P-M-M₄  Ior a stereoisomer or pharmaceutically acceptable salt, solvate, orprodrug form thereof wherein:

M is a 3-10 membered carbocycle or a 4-10 membered heterocycle,consisting of: carbon atoms and 1-3 heteroatoms selected from O,S(O)_(p), N, and NZ²;

ring M is substituted with 0-3 R^(1a) and 0-2 carbonyl groups, and thereare 0-3 ring double bonds;

P is fused onto ring M and is a 5, 6, or 7 membered carbocycle or a 5,6, or 7 membered heterocycle, consisting of: carbon atoms and 1-3heteroatoms selected from O, S(O)_(p), and N;

ring P is substituted with 0-3 R^(1a) and 0-2 carbonyl groups, and thereare 0-3 ring double bonds;

alternatively, ring P is absent and P₄ is directly attached to ring M,provided that when ring P is absent, P₄ and M₄ are attached to the 1,2,1,3, or 1,4 positions of ring M;

one of P₄ and M₄ is -Z-A-B and the other -G₁-G;

G is a group of Formula IIa or IIb:

in formula IIa, ring E is substituted with 1-2 R^(a), provided that atleast one R^(a) is ortho to the point of attachment of ring E;

in formula IIb, ring D is substituted with 1-2 R^(a), provided that atleast one R^(a) is ortho to the point of attachment of ring D;

ring D, including the two atoms of Ring E to which it is attached, is a5-6 membered ring consisting of: carbon atoms and 0-2 heteroatomsselected from the group consisting of N, O, and S(O)_(p);

ring D is substituted with 0-2 R and there are 0-3 ring double bonds;

E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, andpyridazinyl, and is substituted with 0-2 R;

alternatively, ring D is absent and ring E is selected from phenyl,pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrazolyl,imidazolyl, isoxazolyl, oxazolyl, triazolyl, thienyl, and thiazolyl, andring E is substituted with 0-2 R;

alternatively, ring D is absent and ring E is selected from phenyl,pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrazolyl,imidazolyl, isoxazolyl, oxazolyl, triazolyl, thienyl, and thiazolyl, andring E is substituted with 0-1 R and with a 5-6 membered heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p), wherein the 5-6 membered heterocycleis substituted with 0-2 carbonyl and 1-2 R and there are 0-3 ring doublebonds;

R is selected from H, C₁₋₄ alkyl, F, Cl, Br, I, OH, OCH₃, OCH₂CH₃,OCH(CH₃)₂, OCH₂CH₂CH₃, CN, C(═NR⁸)NR⁷R⁹, NHC(═NR⁸)NR⁷R⁹,ONHC(═NR⁸)NR⁷R⁹, NR⁸CH(═NR⁷), NH₂, NH(C₁₋₃ alkyl), N(C₁₋₃ alkyl)₂,C(═NH)NH₂, CH₂NH₂, CH₂NH(C₁₋₃ alkyl), CH₂N(C₁₋₃ alkyl)₂, CH₂CH₂NH₂,CH₂CH₂NH(C₁₋₃ alkyl), CH₂CH₂N(C₁₋₃ alkyl)₂, (CR⁸R⁹)_(t)C(O)H,(CR⁸R⁹)_(t)C(O)R^(2c), (CR⁸R⁹)_(t)NR⁷R⁸, (CR⁸R⁹)_(t)C(O)NR⁷R⁸,(CR⁸R⁹)_(t)NR⁷C(O)R⁷, (CR⁸R⁹)_(t)OR³, (CR⁸R⁹)_(t)S(O)_(p)NR⁷R⁸,(CR⁸R⁹)_(t)NR⁷S(O)_(p)R⁷, (CR⁸R⁹)_(t)SR³, (CR⁸R⁹)_(t)S(O)R³,(CR⁸R⁹)_(t)S(O)₂R³, and OCF₃;

alternatively, when 2 R groups are attached to adjacent atoms, theycombine to form methylenedioxy or ethylenedioxy;

R^(a) is (CR⁸R⁹)₀₋₃R^(b)(CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₄R^(c);

R^(b) is selected from O, C(O), C(O)NR³, C(O)N((CH₂)₁₋₃R³), S(O), S(O)₂,S(O)₂NR³, NR³, NR³C(O), NR³S(O)₂, OC(O)NR³, NR³C(O)NR³, and SC(O)NR³;

R^(c) is selected from H, OR³, NR³C(O)R³, C(O)R³, CO₂R³, C(O)NR³R^(3a),S(O)₂NR³R^(3a), —CN, C₃₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-12membered heterocycle substituted with 0-2 R⁴ and consisting of: carbonatoms and 1-4 heteroatoms selected from the group consisting of N, O,and S(O)_(p);

provided that when the (CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₄ portion ofR^(a) is absent, then R^(c) is selected from NR³C(O)R³, S(O)₂NR³R^(3a),C₃₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-12 membered heterocyclesubstituted with 0-2 R⁴ and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p);

further provided that when the R^(a) is C(O)—NR*R* and NR*R* is aheterocyclic ring, then the heterocyclic ring is substituted with 1-2R⁴;

further provided that the (CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₄R^(c) portionof R^(a) is other than (CR⁸R^(2b))₀₋₃-unsubstituted-phenyl or(CR⁸R⁹)₀₋₃-unsubstituted-phenyl;

A is selected from: C₃₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-12membered heterocycle consisting of: carbon atoms and 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p) and substitutedwith 0-2 R⁴;

B is selected from Y, X—Y, N(B¹)C(O)C(R³R^(3g))₁₋₄NB²B³, C(B⁵)═NB⁴, and

provided that Z and B are attached to different atoms on A and that theR^(4d) shown is other than OH;

B¹ is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, —(CH₂)₀₋₂—C₃₋₇ carbocyclesubstituted with 0-2 R^(4b), and —(CH₂)₀₋₂-5-6 membered heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p) and substituted with 0-2 R^(4b);

B² is selected from H, C₁₋₆ alkyl substituted with 0-2 R^(4c),C(O)R^(2e), C(O)OR^(2d), C(O)NR^(2d)R^(2d), C(O)NH(CH₂)₂NR^(2d)R^(2d),SO₂NR^(2d)R^(2d), C(O)NHSO₂—C₁₋₄ alkyl, and S(O)_(p)R^(5a);

B³ is selected from H, C₁₋₆ alkyl substituted with 0-2 R^(4c),

—(CH₂)₀₋₂-3-6 membered carbocycle substituted with 0-2 R⁵, and a—(CH₂)₀₋₂-4-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-2 R⁵;

B⁴ is selected from H, SO₂R^(3b), C(O)R^(3b), SO₂NR³R^(3b),C(O)NR³R^(3b), OR², SR², —CN, and NO₂;

B⁵ is NR²R^(2f) or CR³R²R^(2f);

Q¹ and Q² are each N;

alternatively, Q¹ is CR³ and R^(4d) is NR²R^(2a) or NR^(3a)B⁴, providedthat when Q¹ is CR³, then this R³ group optionally forms a ring with theR² group of R^(4d), this ring is a 5-6 membered ring consisting of, inaddition to the C—C—N shown, carbon atoms and from 0-1 additionalheteroatoms selected from N, O, and S(O)_(p), and this ring issubstituted with 0-1 R⁵;

ring Q is a 5-8 membered ring consisting of, in addition to the

Q¹-CR^(4d)=Q² group shown, carbon atoms and 0-2 heteroatoms selectedfrom N, O, and S(O)_(p), and the ring is substituted with an additional0-2 R^(4d);

Y is selected from: CY¹Y²R^(4a), NR³R^(3a), C(O)NR³R^(3a), C₃₋₁₀carbocycle substituted 0-2 R⁴ and 0-1 R^(4a), and, 3-10 memberedheterocycle consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p) and substituted with 0-2R⁴ and 0-1 R^(4a);

Y¹ and Y² are independently C₁₋₄ alkyl substituted with 0-2 R⁴;

X is absent or is selected from —(CR²R^(2a))₁₋₄—,—CR²(CR²R^(2b))(CH₂)_(t)—, —C(O)—, —C(═NR^(1b))—, —CR²(NR^(1b)R²)—,—CR²(OR²)—, —CR²(SR²)—, —C(O)CR²R^(2a)—, —CR²R^(2a)C(O), —S(O)—,—S(O)₂—, —SCR²R^(2a)—, —S(O)CR²R^(2a)—, —S(O)₂CR²R^(2a)—,—CR²R^(2a)S(O)—, —CR²R^(2a)S(O)₂—, —S(O)₂NR²CR²R^(2a)—, —NR²S(O)₂—,—CR²R^(2a)NR²S(O)₂—, —NR²S(O)₂CR²R^(2a)—, —NR²C(O)—, —C(O)NR²CR²R^(2a)—,—NR²C(O)CR²R^(2a)—, —CR²R^(2a)NR²C(O)—, —NR²CR²R^(2a)—, and—OCR²R^(2a)—;

G₁ is absent or is selected from (CR³R^(3a))₁₋₅,(CR³R^(3a))₀₋₂CR³═CR³(CR³R^(3a))₀₋₂, (CR³R^(3a))₀₋₂C≡C(CR³R^(3a))₀₋₂,(CR³R^(3a))_(u)C(O)(CR³R^(3a))_(w), (CR³R^(3a))_(u)C(O)O(CR³R^(3a))_(w),(CR³R^(3a))_(u)OC(O)(CR³R^(3a))_(w), (CR³R^(3a))_(u)O(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)C(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)C(O)(CR³R^(3a))_(w),(CR³R^(3a))_(u)OC(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)C(O)O(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)C(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)C(S)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(CR³R^(3a))_(w), (CR³R^(3a))_(u)S(O)(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(O)₂(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)S(O)₂(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(O)₂NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)S(O)₂NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3e)(CR³R^(3a))_(w),(CR³R^(3a))_(u)C(O)(CR³R^(3a))_(u)C(O)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)(CR³R^(3a))_(u)C(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)C(O)(CR³R^(3a))_(u)C(O)(CR³R^(3a))_(w),(CR³R^(3a))_(u)C(O)(CR³R^(3a))_(u)C(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)C(O)(CR³R^(3a))_(u)C(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(O)₂NR^(3b)C(O)(CR³R^(3a))_(w),(CR³R^(3a))_(u)C(O)NR^(3b)S(O)₂(CR³R^(3a))_(w), and(CR³R^(3a))_(u)S(O)₂NR^(3b)C(O)NR^(3b)CR³R^(3a))_(w), wherein u+w total0, 1, 2, 3, or 4 and the right side of G₁ is attached to ring G,provided that G₁ does not form an N—S, NCH₂N, NCH₂O, or NCH₂S bond witheither group to which it is attached;

Z is selected from a bond, —CR³R^(3e))₁₋₄—,(CR³R^(3e))_(q)O(CR³R^(3e))_(q1),(CR³R^(3e))_(q)NR^(3b)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)C(O)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)C(O)O(CR³R^(3e))_(q1),(CR³R^(3e))_(q)OC(O)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)C(O)NR^(3b)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)NR^(3b)C(O)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)OC(O)O(CR³R^(3e))_(q1),(CR³R^(3e))_(q)OC(O)NR^(3b)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)NR^(3b)C(O)O(CR³R^(3e))_(q1),(CR³R^(3e))_(q)NR^(3b)C(O)NR^(3b)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)C(O)(CR³R^(3e))_(q)C(O)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)NR^(3b)(CR³R^(3e))_(q)C(O)NR^(3b)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)NR^(3b)C(O)(CR³R^(3e))_(q)C(O)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)C(O)(CR³R^(3e))_(q)C(O)NR^(3b)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)NR^(3b)C(O)(CR³R^(3e))_(q)C(O)NR^(3b)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)S(CR³R^(3e))_(q1), (CR³R^(3e))_(q)S(O)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)S(O)₂(CR³R^(3e))_(q1),(CR³R^(3e))_(q)SO₂NR^(3b)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)NR^(3b)SO₂(CR³R^(3e))_(q1),(CR³R^(3e))_(q)S(O)₂NR^(3b)C(O)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)C(O)NR^(3b)S(O)₂(CR³R^(3e))_(q1), and(CR³R^(3e))_(q)NR^(3b)SO₂NR^(3b)(CR³R^(3e))_(q1), wherein q+q1 total 0,1, 2, 3, or 4 and the right side of Z is attached to ring A, providedthat Z does not form a N—S, NCH₂N, NCH₂O, or NCH₂S bond with eithergroup to which it is attached;

Z² is selected from H, S(O)₂NHR^(3b), C(O)R^(3b), C(O)NHR^(3b),C(O)OR^(3f), S(O)R^(3f), S(O)₂R^(3f), C₁₋₆ alkyl substituted with 0-2R^(1a), C₂₋₆ alkenyl substituted with 0-2 R^(1a), C₂₋₆ alkynylsubstituted with 0-2 R^(1a), —(C₀₋₄ alkyl)-C₃₋₁₀ carbocycle substitutedwith 0-3 R^(1a), and —(C₀₋₄ alkyl)-5-10 membered heterocycle substitutedwith 0-3 R^(1a) and consisting of: carbon atoms and 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p);

R^(1a), at each occurrence, is selected from H, —(CR³R^(3a))_(r)—R^(1b),—(CR³R^(3a))_(r)—CR³R^(1b)R^(1b),—(CR³R^(3a))_(r)—O—(CR³R^(3a))_(r)—R^(1b),—(CR³R^(3a))_(r)—NR²—(CR³R^(3a))_(r)—R^(1b),—(CR³R^(3a))_(r)—S(O)_(p)—(CR³R^(3a))_(r)—R^(1b),—(CR³R^(3a))_(r)—CO₂—(CR³R^(3a))_(r)—R^(1b),—(CR³R^(3a))_(r)—C(O)NR²—(CR³R^(3a))_(r)—R^(1b),—(CR³R^(3a))_(r)—C(O)—(CR³R^(3a))_(r)—R^(1b), —C₂₋₆ alkenylene-R^(1b),—C₂₋₆ alkynylene-R^(1b), and —(CR³R^(3a))_(r)—C(═NR^(1b))NR³R^(1b),provided that R^(1a) forms other than an N-halo, N—S, O—O, or N—CN bond;

alternatively, when two R^(1a) groups are attached to adjacent atoms,together with the atoms to which they are attached they form a 5-7membered ring consisting of: carbon atoms and 0-2 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), this ring beingsubstituted with 0-2 R^(4b) and 0-3 ring double bonds;

R^(1b) is selected from H, C₁₋₃ alkyl, F, Cl, Br, I, —CN, —NO₂, —CHO,(CF₂)_(r)CF₃, (CR³R^(3a))_(r)OR², NR²R^(2a), C(O)R^(2b), CO₂R^(2b),OC(O)R², CH(CH₂OR²)₂, (CF₂)_(r)CO₂R^(2a), S(O)_(p)R^(2b),NR²(CH₂)_(r)OR², C(═NR^(2c))NR²R^(2a), NR²C(O)R^(2b), NR²C(O)NR²R^(2a),NR²C(O)₂R^(2a), OC(O)NR²R^(2a), C(O)NR²R^(2a), C(O)NR²(CH₂)_(r)OR²,SO₂NR²R^(2a), NR²SO₂R², C(O)NR²SO₂R², C₃₋₆ carbocycle substituted with0-2 R^(4b), and 5-10 membered heterocycle substituted with 0-2 R^(4b)and consisting of carbon atoms and from 1-4 heteroatoms selected fromthe group consisting of N, O, and S(O)_(p), provided that R^(1b) formsother than an O—O, N-halo, N—S, or N—CN bond and provided thatS(O)_(p)R² forms other than S(O)₂H or S(O)H;

R², at each occurrence, is selected from H, CF₃, C₁₋₆ alkyl,—(CH₂)_(r)—C₃₋₁₀ carbocycle substituted with 0-2 R^(4b), and—(CH₂)_(r)-5-10 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),and substituted with 0-2 R^(4b);

R^(2a), at each occurrence, is selected from H, CF₃, C₁₋₆ alkyl,—(CH₂)_(r)—C₃₋₁₀ carbocycle substituted with 0-2 R^(4b), and—(CH₂)_(r)-5-10 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),and substituted with 0-2 R^(4b);

alternatively, NR²R^(2a) forms a 5 or 6 membered saturated, partiallysaturated or unsaturated ring substituted with 0-2 R^(4b) and consistingof: 0-1 additional heteroatoms selected from the group consisting of N,O, and S(O)_(p);

R^(2b), at each occurrence, is selected from CF₃, C₁₋₄ alkoxysubstituted with 0-2 R^(4b), C₁₋₆ alkyl substituted with 0-2 R^(4b),—(CH₂)_(r)—C₃₋₁₀ carbocycle substituted with 0-2 R^(4b), and—(CH₂)_(r)-5-10 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),and substituted with 0-2 R^(4b);

R^(2c), at each occurrence, is selected from CF₃, OH, C₁₋₄ alkoxy, C₁₋₆alkyl, —(CH₂)_(r)—C₃₋₁₀ carbocycle substituted with 0-2 R^(4b), and—(CH₂)_(r)-5-10 membered heterocycle containing from 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p), andsubstituted with 0-2 R^(4b);

R^(2d), at each occurrence, is selected from H, R^(4c), C₁₋₆ alkylsubstituted with 0-2 R^(4c), —(CR³R^(3a))_(r)—C₃₋₁₀ carbocyclesubstituted with 0-2 R^(4c), and —(CR³R^(3a))_(r)-5-10 memberedheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), provided that R^(2d) forms other than a N-halo, N—C-halo,S(O)_(p)-halo, O-halo, N—S, S—N, S(O)_(p)—S(O)_(p), S—O, O—N, O—S, orO—O moiety;

alternatively, NR^(2d)R^(2d) forms a 5-10 membered saturated, partiallysaturated or unsaturated ring substituted with 0-2 R^(4b) and consistingof: 0-1 additional heteroatoms selected from the group consisting of N,O, and S(O)_(p);

R^(2e), at each occurrence, is selected from H, R^(4c), C₁₋₆ alkylsubstituted with 0-2 R^(4c), —(CR³R^(3a))_(r)—C₃₋₁₀ carbocyclesubstituted with 0-2 R^(4c), and —(CR³R^(3a))_(r)-5-10 memberedheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), provided that R^(2e) forms other than a C(O)-halo orC(O)—S(O)_(p) moiety;

R^(2f) at each occurrence, is selected from H, CF₃, C₁₋₄ alkoxysubstituted with 0-2 R^(4b), C₁₋₆ alkyl substituted with 0-2 R^(4b),—(CH₂)_(r)—C₃₋₁₀ carbocycle substituted with 0-2 R^(4b), and—(CH₂)_(r)-5-10 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-2 R^(4b);

alternatively, CR²R^(2f) forms a 5-8 membered ring consisting of: carbonatoms and 0-2 heteroatoms selected from N, O, and S(O)_(p), and thisring is substituted with 0-2 R^(4b);

alternatively, NR²R^(2f) forms a 5-8 membered ring consisting of: carbonatoms and 0-2 additional heteroatoms selected from N, O, and S(O)_(p),and this ring is substituted with 0-2 R^(4b);

alternatively, when B⁴ is SO₂R^(3b) and B⁵ is NR²R^(2f), R^(3b) andR^(2f) combine to form a 5-8 membered ring consisting of: carbon atomsand 0-2 additional heteroatoms selected from N, O, and S(O)_(p), andthis ring is substituted with 0-2 R^(4b);

alternatively, when B⁴ is C(O)R^(3b) and B⁵ is NR²R², R^(3b) and R^(2f)combine to form a 5-8 membered ring consisting of: carbon atoms and 0-2additional heteroatoms selected from N, O, and S(O)_(p), and this ringis substituted with 0-2 R^(4b);

alternatively, when B⁵ is NR²R^(2f), B⁴ and R^(2f) combine to form a 5-8membered ring consisting of: carbon atoms and 0-2 additional heteroatomsselected from N, O, and S(O)_(p), and this ring is substituted with 0-2R^(4b) and the R² group of NR²R^(2f), in addition to the groups recitedbelow, is selected from SO₂R^(3b), C(O)R^(3b), and —CN;

R³, at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, benzyl, andphenyl;

R^(3a), at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, benzyl, andphenyl;

alternatively, R³ and R^(3a), together with the nitrogen atom to whichthey are attached, combine to form a 5 or 6 membered saturated,partially unsaturated, or unsaturated ring consisting of: carbon atoms,the nitrogen atom to which R³ and R^(3a) are attached, and 0-1additional heteroatoms selected from the group consisting of N, O, andS(O)_(p);

R^(3b), at each occurrence, is selected from H, C₁₋₆ alkyl substitutedwith 0-2 R^(1a), C₂₋₆ alkenyl substituted with 0-2 R^(1a), C₂₋₆ alkynylsubstituted with 0-2 R^(1a), —(C₀₋₄ alkyl)-5-10 membered carbocyclesubstituted with 0-3 R^(1a), and —(C₀₋₄ alkyl)-5-10 membered heterocyclesubstituted with 0-3 R^(1a) and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p);

R^(3c), at each occurrence, is selected from CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, benzyl, andphenyl;

R^(3d), at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C₁₋₄ alkyl-phenyl,and C(═O)R^(3c);

R^(3e), at each occurrence, is selected from H, SO₂NHR³, SO₂NR³R³,C(O)R³, C(O)NHR³, C(O)OR^(3f), S(O)R^(3f), S(O)₂R^(3f), C₁₋₆ alkylsubstituted with 0-2 R^(1a), C₂₋₆ alkenyl substituted with 0-2 R^(1a),C₂₋₆ alkynyl substituted with 0-2 R^(1a), —(C₀₋₄ alkyl)-5-10 memberedcarbocycle substituted with 0-3 R^(1a), and —(C₀₋₄ alkyl)-5-10 memberedheterocycle substituted with 0-3 R^(1a) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p);

R^(3f), at each occurrence, is selected from: C₁₋₆ alkyl substitutedwith 0-2 R^(1a), C₂₋₆ alkenyl substituted with 0-2 R^(1a), C₂₋₆ alkynylsubstituted with 0-2 R^(1a), —(C₀₋₄ alkyl)-5-10 membered carbocyclesubstituted with 0-3 R^(1a), and —(C₀₋₄ alkyl)-5-10 membered heterocyclesubstituted with 0-3 R^(1a) and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p);

R^(3g), at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃,—(CH₂)_(r)-3-6 membered carbocycle, and —(CH₂)_(r)-5-6 memberedheterocycle consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p);

alternatively, CR³R^(3g) forms a cyclopropyl group;

R⁴, at each occurrence, is selected from ═O, CHO, (CR³R^(3a))_(r)OR²,(CR³R^(3a))_(r)F, (CR³R^(3a))_(r)Cl, (CR³R^(3a))_(r)Br,(CR³R^(3a))_(r)I, C₁₋₄ alkyl, (CR³R^(3a))_(r)CN, (CR³R^(3a))_(r)NO₂,(CR³R^(3a))_(r)NR²R^(2a), (CR³R^(3a))_(r)C(O)R^(2c),(CR³R^(3a))_(r)NR²C(O)R^(2b), (CR³R^(3a))_(r)C(O)NR²R^(2a),(CR³R^(3a))_(r)NR²C(O)NR²R^(2a), (CR³R^(3a))_(r)C(═NR²)NR²R^(2a),(CR³R^(3a))_(r)C(═NS(O)₂R⁵)NR²R^(2a),(CR³R^(3a))_(r)NR²C(═NR²)NR²R^(2a),(CR³R^(3a))_(r)C(O)NR²C(═NR²)NR²R^(2a), (CR³R^(3a))_(r)SO₂NR²R^(2a),(CR³R^(3a))_(r)NR²SO₂NR²R^(2a), (CR³R^(3a))_(r)NR²SO₂—C₁₋₄ alkyl,(CR³R^(3a))_(r)NR²SO₂R⁵, (CR³R^(3a))_(r)S(O)_(p)R^(5a),(CR³R^(3a))_(r)(CF₂)_(r)CF₃, NHCH₂R^(1b), OCH₂R^(1b), SCH₂R^(1b),NH(CH₂)₂(CH₂)_(t)R^(1b), O(CH₂)₂(CH₂)_(t)R^(1b), S(CH₂)₂(CH₂)_(t)R^(1b),(CR³R^(3a))_(r)-5-6 membered carbocycle substituted with 0-1 R⁵, and a(CR³R^(3a))_(r)-5-6 membered heterocycle consisting of: carbon atoms and1-4 heteroatoms selected from the group consisting of N, O, and S(O)_(p)and substituted with 0-1 R⁵;

R^(4a) is selected from C₁₋₆ alkyl substituted with 0-2 R^(4c), C₂₋₆alkenyl substituted with 0-2 R^(4c), C₂₋₆ alkynyl substituted with 0-2R^(4c), —(CR³R^(3g))_(r)—C₅₋₁₀ membered carbocycle substituted with 0-3R^(4c), —(CR³R^(3g))_(r)-5-10 membered heterocycle substituted with 0-3R^(4c) and consisting of: carbon atoms and 1-4 heteroatoms selected fromthe group consisting of N, O, and S(O)_(p), (CR³R^(3g))_(r)CN,(CR³R^(3g))_(r)C(═NR^(2d))NR^(2d)R^(2d),(CR³R^(3g))_(r)NR^(2d)C(═NR^(2d))NR^(2d)R^(2d),(CR³R^(3g))_(r)NR^(2d)C(R^(2e))(═NR^(2d)), (CR³R^(3g))_(r)NR^(2d)R^(2d),(CR³R^(3g))_(r)N(→O)R^(2d)R^(2d), (CR³R^(3g))_(r)OR^(2d),(CR³R^(3g))_(r)—NR^(2d)C(O)R^(2e), (CR³R^(3g))_(r)—C(O)R^(2e),(CR³R^(3g))_(r)—OC(O)R^(2e), (CR³R^(3g))_(r)—C(O)NR^(2d)R^(2d),(CR³R^(3g))_(r)—C(O)OR^(2d), (CR³R^(3g))_(r)—NR^(2d)C(O)NR^(2d)R^(2d),(CR³R^(3g))_(r)—OC(O)NR^(2d)R^(2d), (CR³R^(3g))_(r)—NR^(2d)C(O)OR^(2d),(CR³R^(3g))_(r)—SO₂NR^(2d)R^(2d),(CR³R^(3g))_(r)—NR^(2d)SO₂NR^(2d)R^(2d),(CR³R^(3g))_(r)—C(O)NR^(2d)SO₂R^(2d), (CR³R^(3g))_(r)—NR^(2d)SO₂R^(2d),and (CR³R^(3g))_(r)—S(O)_(p)R^(2d), provided that S(O)_(p)R^(2d) formsother than S(O)₂H or S(O)H and further provided that R^(4a) is otherthan a hydroxamic acid;

R^(4b), at each occurrence, is selected from H, ═O, (CH₂)_(r)OR³,(CH₂)_(r)F, (CH₂)_(r)Cl, (CH₂)_(r)Br, (CH₂)_(r)I, C₁₋₄ alkyl,(CH₂)_(r)CN, (CH₂)_(r)NO₂, (CH₂)_(r)NR³R^(3a), (CH₂)_(r)C(O)R³,(CH₂)_(r)C(O)OR^(3c), (CH₂)_(r)NR³C(O)R^(3a), (CH₂)_(r)—C(O)NR³R^(3a),(CH₂)_(r)NR³C(O)NR³R^(3a), (CH₂)_(r)—C(═NR³)NR³R^(3a),(CH₂)_(r)NR³C(═NR³)NR³R^(3a), (CH₂)_(r)SO₂NR³R^(3a),(CH₂)_(r)NR³SO₂NR³R^(3a), (CH₂)_(r)NR³SO₂—C₁₋₄ alkyl,(CH₂)_(r)NR³SO₂CF₃, (CH₂)_(r)NR³SO₂-phenyl, (CH₂)_(r)S(O)_(p)CF₃,(CH₂)_(r)S(O)_(p)—C₁₋₄ alkyl, (CH₂)_(r)S(O)_(p)-phenyl, and(CH₂)_(r)(CF₂)_(r)CF₃;

R^(4c), at each occurrence, is selected from ═O, (CR³R^(3a))_(r)OR²,(CR³R^(3a))_(r)F, (CR³R^(3a))_(r)Br, (CR³R^(3a))_(r)Cl,(CR³R^(3a))_(r)CF₃, C₁₋₄ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,(CR³R^(3a))_(r)CN, (CR³R^(3a))_(r)NO₂, (CR³R^(3a))_(r)NR²R^(2a),(CR³R^(3a))_(r)N(→O)R²R^(2a), (CR³R^(3a))_(r)C(O)R^(2c),(CR³R^(3a))_(r)NR²C(O)R^(2b), (CR³R^(3a))_(r)C(O)NR²R^(2a),(CR³R^(3a))_(r)N═CHOR³, (CR³R^(3a))_(r)C(O)NR²(CH₂)₂NR²R^(2a),(CR³R^(3a))_(r)NR²C(O)NR²R^(2a), (CR³R^(3a))_(r)C(═NR²)NR²R^(2a),(CR³R^(3a))_(r)NR²C(═NR²)NR²R^(2a), (CR³R^(3a))_(r)SO₂NR²R^(2a),(CR³R^(3a))_(r)NR²SO₂NR²R^(2a), (CR³R^(3a))_(r)C(O)NR²SO₂—C₁₋₄ alkyl,(CR³R^(3a))_(r)NR²SO₂R^(5a), (CR³R^(3a))_(r)C(O)NR²SO₂R^(5a),(CR³R^(3a))_(r)S(O)_(p)R^(5a), (CF₂)_(r)CF₃, (CR³R^(3a))_(r)C₃₋₁₀carbocycle substituted with 0-2 R^(4b), and (CR³R^(3a))_(r)4-10 memberedheterocycle substituted with 0-2 R^(4b) and consisting of carbon atomsand from 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p);

R^(4d), at each occurrence, is selected from H, (CR³R^(3a))_(r)OR²,(CR³R^(3a))_(r)F, (CR³R^(3a))_(r)Br, (CR³R^(3a))_(r)Cl, C₁₋₄ alkyl,(CR³R^(3a))_(r)CN, (CR³R^(3a))_(r)NO₂, (CR³R^(3a))_(r)NR²R^(2a),(CR³R^(3a))_(r)C(O)R^(2c), (CR³R^(3a))_(r)NR²C(O)R^(2b),(CR³R^(3a))_(r)C(O)NR²R^(2a), (CR³R^(3a))_(r)N═CHOR³,(CR³R^(3a))_(r)C(O)NH(CH₂)₂NR²R^(2a), (CR³R^(3a))_(r)NR²C(O)NR²R^(2a),(CR³R^(3a))_(r)C(═NR²)NR²R^(2a), (CR³R^(3a))_(r)NHC(═NR²)NR²R^(2a),(CR³R^(3a))_(r)SO₂NR²R^(2a), (CR³R^(3a))_(r)NR²SO₂NR²R^(2a),(CR³R^(3a))_(r)NR²SO₂—C₁₋₄ alkyl, (CR³R^(3a))_(r)C(O)NHSO₂—C₁₋₄ alkyl,(CR³R^(3a))NR²SO₂R⁵, (CR³R^(3a))_(r)S(O)_(p)R^(5a),(CR³R^(3a))_(r)(CF₂)_(r)CF₃, (CR³R^(3a))_(r)-5-6 membered carbocyclesubstituted with 0-1 R⁵, and a (CR³R^(3a))_(r)-5-6 membered heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p) and substituted with 0-1 R⁵;

R⁵, at each occurrence, is selected from H, C₁₋₆ alkyl, ═O,(CH₂)_(r)OR³, F, Cl, Br, I, —CN, NO₂, (CH₂)_(r)NR³R^(3a),(CH₂)_(r)C(O)R³, (CH₂)_(r)C(O)OR^(3c), (CH₂)_(r)NR³C(O)R^(3a),(CH₂)_(r)C(O)NR³R^(3a), (CH₂)_(r)NR³C(O)NR³R^(3a),(CH₂)_(r)CH(═NOR^(3d)), (CH₂)_(r)C(═NR³)NR³R^(3a),(CH₂)_(r)NR³C(═NR³)NR³R^(3a), (CH₂)_(r)SO₂NR³R^(3a),(CH₂)_(r)NR³SO₂NR³R^(3a), (CH₂)_(r)NR³SO₂—C₁₋₄ alkyl,(CH₂)_(r)NR³SO₂CF₃, (CH₂)_(r)NR³SO₂-phenyl, (CH₂)_(r)S(O)_(p)CF₃,(CH₂)_(r)S(O)_(p)—C₁₋₄ alkyl, (CH₂)_(r)S(O)_(p)-phenyl, (CF₂)_(r)CF₃,phenyl substituted with 0-2 R⁶, naphthyl substituted with 0-2 R⁶, andbenzyl substituted with 0-2 R⁶;

R^(5a), at each occurrence, is selected from C₁₋₆ alkyl, (CH₂)_(r)OR³,(CH₂)_(r)NR³R^(3a), (CH₂)_(r)C(O)R³, (CH₂)_(r)C(O)OR^(3c),(CH₂)_(r)NR³C(O)R^(3a), (CH₂)_(r)C(O)NR³R^(3a), (CF₂)_(r)CF₃, phenylsubstituted with 0-2 R⁶, naphthyl substituted with 0-2 R⁶, and benzylsubstituted with 0-2 R⁶, provided that R^(5a) does not form a S—N orS(O)_(p)—C(O) bond;

R⁶, at each occurrence, is selected from H, OH, (CH₂)_(r)OR², halo, C₁₋₄alkyl, CN, NO₂, (CH₂)_(r)NR²R^(2a), (CH₂)_(r)C(O)R^(2b), NR²C(O)R^(2b),NR²C(O)NR²R^(2a), C(═NH)NH₂, NHC(═NH)NH₂, SO₂NR²R^(2a), NR²SO₂NR²R^(2a),and NR²SO₂C₁₋₄ alkyl;

R⁷, at each occurrence, is selected from H, OH, C₁₋₆ alkyl, C₁₋₆alkyl-C(O)—, C₁₋₆ alkyl-O—, (CH₂)_(n)-phenyl, C₁₋₄ alkyl-OC(O)—, C₆₋₁₀aryl-O—, C₆₋₁₀ aryl-OC(O)—, C₆₋₁₀ aryl-CH₂—C(O)—, C₁₋₄ alkyl-C(O)O—C₁₋₄alkyl-OC(O)—, C₆₋₁₀ aryl-C(O)O—C₁₋₄ alkyl-OC(O)—, C₁₋₆ alkyl-NH₂—C(O)—,phenyl-NH₂—C(O)—, and phenyl-C₁₋₄ alkyl-C(O)—;

R⁸, at each occurrence, is selected from H, C₁₋₆ alkyl, and(CH₂)_(n)-phenyl;

alternatively, R⁷ and R⁸, when attached to the same nitrogen, combine toform a 5-10 membered heterocyclic ring consisting of carbon atoms and0-2 additional heteroatoms selected from the group consisting of N, O,and S(O)_(p);

R⁹, at each occurrence, is selected from H, C₁₋₆ alkyl, and(CH₂)_(n)-phenyl;

n, at each occurrence, is selected from 0, 1, 2, and 3;

p, at each occurrence, is selected from 0, 1, and 2;

r, at each occurrence, is selected from 0, 1, 2, 3, 4, 5, and 6; and

t, at each occurrence, is selected from 0, 1, 2, and 3.

In a second embodiment, the present invention provides a novel compoundof Formula II:

or a stereoisomer or pharmaceutically acceptable salt, solvate, orprodrug form thereof, wherein:

ring M, including P₁, P₂, M₁, and M₂, is a 5, 6, or 7 memberedcarbocycle or a 5, 6, or 7 membered heterocycle, consisting of: carbonatoms and 1-3 heteroatoms selected from O, S(O)_(p), N, and NZ²;

ring M is substituted with 0-2 R^(1a) and 0-2 carbonyl groups, and thereare 0-3 ring double bonds;

ring P, including P₁, P₂, and P₃, is a 5 or 6 membered aromaticheterocycle, consisting of: carbon atoms and 1-3 heteroatoms selectedfrom O, S(O)_(p), and N;

alternatively, ring P, including P₁, P₂, and P₃, is a 5 or 6 membereddihydro-aromatic heterocycle, consisting of: carbon atoms and 1-3heteroatoms selected from O, S(O)_(p), and N;

ring P is substituted with 0-2 R^(1a);

one of P₄ and M₄ is -Z-A-B and the other -G₁-G;

G is a group of Formula IIa or IIb:

in formula IIa, ring E is substituted with 1-2 R^(a), provided that atleast one R^(a) is ortho to the point of attachment of ring E;

in formula IIb, ring D is substituted with 1-2 R^(a), provided that atleast one R^(a) is ortho to the point of attachment of ring D;

ring D, including the two atoms of Ring E to which it is attached, is a5-6 membered ring consisting of: carbon atoms and 0-2 heteroatomsselected from the group consisting of N, O, and S(O)_(p);

ring D is substituted with 0-2 R and there are 0-3 ring double bonds;

E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, andpyridazinyl, and is substituted with 0-2 R;

alternatively, ring D is absent, and ring E is selected from phenyl,pyridyl, pyrimidyl, and thienyl, and ring E is substituted with 0-2 R;

alternatively, ring D is absent, ring E is selected from phenyl,pyridyl, and thienyl, and ring E is substituted with 0-2 R and a 5-6membered heterocycle consisting of: carbon atoms and 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p), wherein the5-6 membered heterocycle is substituted with 0-2 carbonyl and 1-2 R andthere are 0-3 ring double bonds;

R is selected from H, C₁₋₄ alkyl, F, Cl, OH, OCH₃, OCH₂CH₃, OCH(CH₃)₂,CN, C(═NH)NH₂, C(═NH)NHOH, C(═NH)NHOCH₃, NH₂,

NH(C₁₋₃ alkyl), N(C₁₋₃ alkyl)₂, C(═NH)NH₂, CH₂NH₂, CH₂NH(C₁₋₃ alkyl),CH₂N(C₁₋₃ alkyl)₂, (CR⁸R⁹)_(t)NR⁷R⁸, C(O)NR⁷R⁸, CH₂C(O)NR⁷R⁸,S(O)_(p)NR⁷R⁸, CH₂S(O)_(p)NR⁷R⁸, SO₂R³, and OCF₃;

alternatively, when 2 R groups are attached to adjacent atoms, theycombine to form methylenedioxy or ethylenedioxy;

R^(a) is (CR⁸R⁹)₀₋₁R^(b)(CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₁R^(c);

R^(b) is selected from O, C(O), C(O)NR³, C(O)N((CH₂)₂₋₃R³), S(O), S(O)₂,S(O)₂NR³, NR³, NR³C(O), and NR³S(O)₂;

R^(c) is selected from H, OR³, NR³C(O)R³, C(O)R³, CO₂R³, C(O)NR³R^(3a),S(O)₂NR³R^(3a), —CN, C₃₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-12membered heterocycle substituted with 0-2 R⁴ and consisting of: carbonatoms and 1-4 heteroatoms selected from the group consisting of N, O,and S(O)_(p);

R^(c) is selected from H, OR³, NR³C(O)R³, C(O)R³, CO₂R³, C(O)NR³R^(3a),S(O)₂NR³R^(3a), C₅₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-10membered heterocycle substituted with 0-2 R⁴ and consisting of: carbonatoms and 1-4 heteroatoms selected from the group consisting of N, O,and S(O)_(p);

provided that when the (CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₁ portion ofR^(a) is absent, then R^(c) is selected from NR³C(O)R³, S(O)₂NR³R^(3a),C₅₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-10 membered heterocyclesubstituted with 0-2 R⁴ and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p);

further provided that when the R^(a) is C(O)—NR*R* and NR*R* is aheterocyclic ring, then the heterocyclic ring is substituted with 1-2R⁴;

further provided that the (CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₄R^(c) portionof R^(a) is other than (CR⁸R^(2b))₀₋₃-unsubstituted-phenyl or(CR⁸R⁹)₀₋₃-unsubstituted-phenyl;

A is selected from: C₅₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-10membered heterocycle consisting of: carbon atoms and 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p) and substitutedwith 0-2 R⁴;

B is selected from Y, X—Y, N(B¹)C(O)C(R³R^(3g))NB²B³,N(B¹)C(O)C(R³R^(3g))C(R³R^(3g))NB²B³,

provided that Z and B are attached to different atoms on A, the R^(4d)shown is other than OH, and that the A-X—N moiety forms other than aN—N—N group;

B¹ is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, —(CH₂)₀₋₁—C₃₋₇ carbocyclesubstituted with 0-2 R^(4b), and —(CH₂)₀₋₁-5-6 membered heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p) and substituted with 0-2 R^(4b);

B² is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, NR^(2d)R^(2d), CH₂—NR^(2d)R^(2d),CH₂CH₂—NR^(2d)R^(2d), C(O)R^(2e), C(O)NR^(2d)R^(2d), SO₂NR^(2d)R^(2d),and S(O)_(p)R^(5a);

B³ is selected from H, C₁₋₆ alkyl substituted with 0-1 R^(4c),—(CH₂)₀₋₁-3-6 membered carbocycle substituted with 0-1 R⁵, and a—(CH₂)₀₋₁-5-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-1 R⁵;

B⁴ is selected from H, SO₂R^(3b), C(O)R^(3b), SO₂NR³R^(3b),C(O)NR³R^(3b), OR², and —CN;

B⁵ is NR²R^(2f) or CR³R²R^(2f);

ring Q is a 5-6 membered ring consisting of, in addition to theQ¹-CR^(4d)=Q² group shown, carbon atoms and 0-2 heteroatoms selectedfrom N, O, and S(O)_(p), and the ring is substituted with an additional0-2 R^(4d);

Q¹ and Q² are each N;

alternatively, Q¹ is CR³ and R^(4d) is NR²R^(2a) or NR^(3a)B⁴, providedthat when Q¹ is CR³, then this R³ group optionally forms a ring with theR² group of R^(4d), this ring is a 5-6 membered ring consisting of, inaddition to the C—C—N shown, carbon atoms and from 0-1 additionalheteroatoms selected from N, O, and S(O)_(p), and this ring issubstituted with 0-1 R⁵;

Q⁴ is selected from C═O and SO₂;

ring Q³ is a 4-7 membered monocyclic or tricyclic ring consisting of, inaddition to the N-Q⁴ group shown, carbon atoms and 0-2 heteroatomsselected from NR^(4c), O, S, S(O), and S(O)₂, wherein: 0-2 double bondsare present within the ring and the ring is substituted with 0-2 R⁴;

alternatively, ring Q³ is a 4-7 membered ring to which another ring isfused, wherein: the 4-7 membered ring consists of, in addition to theshown amide group, carbon atoms and 0-2 heteroatoms selected fromNR^(4c), O, S, S(O), and S(O)₂ and 0-1 double bonds are present withinthe ring; the fusion ring is phenyl or a 5-6 membered heteroaromaticconsisting of carbon atoms and 1-2 heteroatoms selected from NR^(4c), O,and S;

ring Q³, which includes the 4-7 membered ring and the fusion ring, issubstituted with 0-3 R⁴;

ring Q⁵ is a C₃₋₇ monocyclic carbocycle or 3-7 membered monocyclicheterocycle, wherein the carbocycle or heterocycle consists of: carbonatoms and 0-2 heteroatoms selected from N, O, and S(O)_(p), thecarbocycle or heterocycle further comprises 0-2 double bonds and 0-2carbonyl groups, and the carbocycle or heterocycle is substituted with0-2 R⁴;

X is selected from —(CR²R^(2a))₁₋₄—, —C(O)—, —C(═NR^(1c))—,—CR²(NR^(1b)R²)—, —C(O)CR²R^(2a)—, —CR²R^(2a)C(O), —C(O)NR²—, —NR²C(O)—,—C(O)NR²CR²R^(2a)—, —NR²C(O)CR²R^(2a)—, —CR²R^(2a)C(O)NR²—,—CR²R^(2a)NR²C(O)—, —NR²C(O)NR²—, —NR²—, —NR²CR²R^(2a)—, —CR²R^(2a)NR²—,—S(O)₂—, —NR²S(O)₂—, O, —CR²R^(2a)O—, and —OCR²R^(2a)—;

Y is selected from: CY¹Y²R^(4a), NR³R^(3a), and C(O)NR³R^(3a);

Y¹ and Y² are independently C₁₋₃ alkyl substituted with 0-2 R⁴;

alternatively, Y is selected from one of the following carbocyclic andheterocycles that are substituted with 1 R^(4a) and 0-2 R⁴: cyclopropyl,cyclopentyl, cyclohexyl, phenyl, piperidinyl, piperazinyl, pyridyl,pyrimidyl, furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl,oxazolyl, isoxazolyl, isoxazolinyl, thiazolyl, isothiazolyl, pyrazolyl,imidazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl,1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl,1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl,1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, benzofuranyl,benzothiofuranyl, indolyl, benzimidazolyl, benzoxazolyl, benzthiazolyl,indazolyl, benzisoxazolyl, benzisothiazolyl, and isoindazolyl;

Z is selected from a bond, CH₂, CH₂CH₂, CH₂O, OCH₂, C(O), NH, CH₂NH,NHCH₂, CH₂C(O), C(O)CH₂, C(O)NH, NHC(O), NHC(O)CH₂C(O)NH, S(O)₂,CH₂S(O)₂, S(O)₂(CH₂), SO₂NH, and NHSO₂, wherein the right side of Z isattached to ring A, provided that Z does not form a N—S, NCH₂N, NCH₂O,or NCH₂S bond with either group to which it is attached;

Z² is selected from H, C₁₋₄ alkyl, phenyl, benzyl, C(O)R^(3b),S(O)R^(3f), and S(O)₂R^(3f);

R^(1a), at each occurrence, is selected from H, —(CH₂)_(r)—R^(1b),—(CH(CH₃))_(r)—R^(1b), —(C(CH₃)₂)_(r)—R^(1b), —O—(CR³R^(3a))_(r)—R^(1b),—NR²—(CR³R^(3a))_(r)—R^(1b), and —S—(CR³R^(3a))_(r)—R^(1b), providedthat R^(1a) forms other than an N-halo, N—S, O—O, or N—CN bond;

alternatively, when two R^(1a) groups are attached to adjacent atoms,together with the atoms to which they are attached they form a 5-7membered ring consisting of: carbon atoms and 0-2 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), this ring beingsubstituted with 0-2 R^(4b) and 0-3 ring double bonds;

R^(1b) is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, F, Cl, Br,I, —CN, —CHO, CF₃, OR², NR²R^(2a), C(O)R^(2b), CO₂R^(2b), OC(O)R²,CO₂R^(2a), S(O)_(p)R², NR²(CH₂)_(r)OR², NR²C(O)R^(2b), NR²C(O)NHR²,NR²C(O)₂R^(2a), OC(O)NR²R^(2a), C(O)NR²R^(2a), C(O)NR²(CH₂)_(r)OR²,SO₂NR²R^(2a), NR²SO₂R², C₅₋₆ carbocycle substituted with 0-2 R^(4b), and5-6 membered heterocycle consisting of carbon atoms and from 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),and substituted with 0-2 R^(4b), provided that R^(1b) forms other thanan O—O, N-halo, N—S, or N—CN bond;

R², at each occurrence, is selected from H, CF₃, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, benzylsubstituted with 0-2 R^(4b), C₅₋₆ carbocycle substituted with 0-2R^(4b), a C₅₋₆ carbocyclic-CH₂-group substituted with 0-2 R^(4b), and5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p), andsubstituted with 0-2 R^(4b);

R^(2a), at each occurrence, is selected from H, CF₃, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃,benzyl substituted with 0-2 R^(4b), C₅₋₆ carbocycle substituted with 0-2R^(4b), and 5-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),and substituted with 0-2 R^(4b);

alternatively, NR²R^(2a) forms a 5 or 6 membered saturated, partiallysaturated or unsaturated ring substituted with 0-2 R^(4b) and consistingof: 0-1 additional heteroatoms selected from the group consisting of N,O, and S(O)_(p);

R^(2b), at each occurrence, is selected from CF₃, C₁₋₄ alkoxy, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃,C(CH₃)₃, benzyl substituted with 0-2 R^(4b), C₅₋₆ carbocycle substitutedwith 0-2 R^(4b), and 5-6 membered heterocycle consisting of: carbonatoms and 1-4 heteroatoms selected from the group consisting of N, O,and S(O)_(p), and substituted with 0-2 R^(4b);

R^(2c), at each occurrence, is selected from CF₃, OH, C₁₋₄ alkoxy, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃,C(CH₃)₃, benzyl substituted with 0-2 R^(4b), C₅₋₆ carbocycle substitutedwith 0-2 R^(4b), and 5-6 membered heterocycle containing from 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),and substituted with 0-2 R^(4b);

R^(2d), at each occurrence, is selected from H, R^(4c), C₁₋₄ alkylsubstituted with 0-2 R^(4c), —(CR³R^(3a))_(r)—C₃₋₆ carbocyclesubstituted with 0-2 R^(4c), and —(CR³R^(3a))_(r)-5-6 memberedheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), provided that R^(2d) forms other than a N-halo, N—C-halo,S(O)_(p)-halo, O-halo, N—S, S—N, S(O)_(p)—S(O)_(p), S—O, O—N, O—S, orO—O moiety;

alternatively, NR^(2d)R^(2d) forms a 5 or 6 membered saturated,partially saturated or unsaturated ring substituted with 0-2 R^(4b) andconsisting of: 0-1 additional heteroatoms selected from the groupconsisting of N, O, and S(O)_(p);

R^(2e), at each occurrence, is selected from H, R^(4c), C₁₋₄ alkylsubstituted with 0-2 R^(4c), —(CR³R^(3a))_(r)—C₃₋₆ carbocyclesubstituted with 0-2 R^(4c), and —(CR³R^(3a))_(r)-5-6 memberedheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), provided that R^(2e) forms other than a C(O)-halo orC(O)—S(O)_(p) moiety;

R^(2f) at each occurrence, is selected from H, CF₃, C₁₋₄ alkoxy, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃,C(CH₃)₃, benzyl substituted with 0-1 R^(4b), C₅₋₆ carbocycle substitutedwith 0-2 R^(4b), and 5-6 membered heterocycle containing from 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-2 R^(4b);

alternatively, CR²R^(2f) forms a 5-6 membered ring consisting of: carbonatoms and 0-2 heteroatoms selected from N, O, and S(O)_(p), and thisring is substituted with 0-2 R^(4b);

alternatively, NR²R^(2f) forms a 5-6 membered ring consisting of: carbonatoms and 0-2 additional heteroatoms selected from N, O, and S(O)_(p),and this ring is substituted with 0-2 R^(4b);

alternatively, when B⁵ is NR²R^(2f), B⁴ and R^(2f) combine to form a 5-6membered ring consisting of: carbon atoms and 0-2 additional heteroatomsselected from N, O, and S(O)_(p), and this ring is substituted with 0-2R^(4b) and the R² group of NR²R^(2f), in addition to the groups recitedbelow, is selected from SO₂R^(3b) and C(O)R^(3b);

R³, at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, benzyl, and phenyl;

R^(3a), at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, benzyl, and phenyl;

alternatively, R³ and R^(3a), together with the nitrogen atom to whichthey are attached, combine to form a 5 or 6 membered saturated,partially unsaturated, or unsaturated ring consisting of: carbon atomsand the nitrogen atom to which R³ and R^(3a) are attached;

R^(3b), at each occurrence, is selected from H, CF₃, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, —(C₀₋₁ alkyl)-5-6 membered carbocycle substitutedwith 0-1 R^(1a), and —(C₀₋₁ alkyl)-5-6 membered heterocycle substitutedwith 0-1 R^(1a) and consisting of: carbon atoms and 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p);

R^(3c), at each occurrence, is selected from CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, benzyl, and phenyl;

R^(3d), at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂-phenyl, CH₂CH₂-phenyl, and C(═O)R^(3c);

R⁴, at each occurrence, is selected from ═O, OR², CH₂OR², (CH₂)₂OR², F,Cl, Br, I, C₁₋₄ alkyl, —CN, NO₂, NR²R^(2a), CH₂NR²R^(2a),(CH₂)₂NR²R^(2a), C(O)R^(2c), NR²C(O)R^(2b), C(O)NR²R^(2a),NR²C(O)NR²R^(2a), SO₂NR²R^(2a), NR²SO₂NR²R^(2a), S(O)_(p)R^(5a),NR²SO₂—C₁₋₄ alkyl, NR²SO₂R⁵, CF₃, CF₂CF₃, 5-6 membered carbocyclesubstituted with 0-1 R⁵, and a 5-6 membered heterocycle consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p), and substituted with 0-1 R⁵;

R^(4b), at each occurrence, is selected from H, ═O, OR³, CH₂OR³, F, Cl,CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂,CH(CH₃)CH₂CH₃, C(CH₃)₃, —CN, NO₂, NR³R^(3a), CH₂NR³R^(3a), C(O)R³,CH₂—C(O)R³, C(O)OR^(3c), CH₂C(O)OR^(3c), NR³C(O)R^(3a),CH₂NR³C(O)R^(3a), C(O)NR³R^(3a), CH₂C(O)NR³R^(3a), NR³C(O)NR³R^(3a),CH₂NR³C(O)NR³R^(3a), C(═NR³)NR³R^(3a), CH₂C(═NR³)NR³R^(3a),NR³C(═NR³)NR³R^(3a), CH₂NR³C(═NR³)NR³R^(3a), SO₂NR³R^(3a),CH₂SO₂NR³R^(3a), NR³SO₂NR³R^(3a), CH₂NR³SO₂NR³R^(3a), NR³SO₂—C₁₋₄ alkyl,CH₂NR³SO₂—C₁₋₄ alkyl, NR³SO₂CF₃, CH₂NR³SO₂CF₃, NR³SO₂-phenyl,CH₂NR³SO₂-phenyl, S(O)_(p)CF₃, CH₂S(O)_(p)CF₃, S(O)_(p)—C₁₋₄ alkyl,CH₂S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl, CH₂S(O)_(p)-phenyl, CF₃, andCH₂—CF₃;

R^(4c), at each occurrence, is selected from ═O, (CR³R^(3a))_(r)OR²,(CR³R^(3a))_(r)F, (CR³R^(3a))_(r)Br, (CR³R^(3a))_(r)Cl,(CR³R^(3a))_(r)CF₃, C₁₋₄ alkyl, C₂₋₃ alkenyl, C₂₋₃ alkynyl,(CR³R^(3a))_(r)CN, (CR³R^(3a))_(r)NO₂, (CR³R^(3a))_(r)NR²R^(2a),(CR³R^(3a))_(r)N(→O)R²R^(2a), (CR³R^(3a))_(r)C(O)R^(2c),(CR³R^(3a))_(r)NR²C(O)R^(2b), (CR³R^(3a))_(r)C(O)NR²R^(2a),(CR³R^(3a))_(r)NR²C(O)NR²R^(2a), (CR³R^(3a))_(r)SO₂NR²R^(2a),(CR³R^(3a))_(r)NR²SO₂NR²R^(2a), (CR³R^(3a))_(r)NR²SO₂R^(5a),(CR³R^(3a))_(r)C(O)NR²SO₂R^(5a), (CR³R^(3a))_(r)S(O)_(p)R^(5a),(CF₂)_(r)CF₃, (CR³R^(3a))_(r)C₃₋₁₀ carbocycle substituted with 0-2R^(4b), and (CR³R^(3a))_(r)5-10 membered heterocycle consisting ofcarbon atoms and from 1-4 heteroatoms selected from the group consistingof N, O, and S(O)_(p) and substituted with 0-2 R^(4b);

R^(4d), at each occurrence, is selected from H, CH₂OR², OR², C₁₋₄ alkyl,CH₂—CN, —CN, CH₂NO₂, NO₂, CH₂NR²R^(2a), NR²R^(2a), CH₂—C(O)R^(2c),C(O)R^(2c), NR²C(O)R^(2b), (CH₂)_(r)C(O)NR²R^(2a), NR²C(O)NR²R^(2a),(CH₂)_(r)SO₂NR²R^(2a), NR²SO₂NR²R^(2a), NR²SO₂R⁵,(CH₂)_(r)S(O)_(p)R^(5a), CH₂CF₃, CF₃, CH₂-5-6 membered carbocyclesubstituted with 0-1 R⁵, 5-6 membered carbocycle substituted with 0-1R⁵, a CH₂-5-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-1 R⁵, and a 5-6 membered heterocycle consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p) and substituted with 0-1 R⁵;

R⁵, at each occurrence, is selected from H, ═O, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, OR³,CH₂OR³, F, Cl, —CN, NO₂, NR³R^(3a), CH₂NR³R^(3a), C(O)R³, CH₂C(O)R³,C(O)OR^(3c), CH₂C(O)OR^(3c), NR³C(O)R^(3a), C(O)NR³R^(3a),NR³C(O)NR³R^(3a), CH(═NOR^(3d)), C(═NR³)NR³R^(3a), NR³C(═NR³)NR³R^(3a),SO₂NR³R^(3a), NR³SO₂NR³R^(3a), NR³SO₂—C₁₋₄ alkyl, NR³SO₂CF₃,NR³SO₂-phenyl, S(O)_(p)CF₃, S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl, CF₃,phenyl substituted with 0-2 R⁶, naphthyl substituted with 0-2 R⁶, andbenzyl substituted with 0-2 R⁶;

R^(5a), at each occurrence, is selected from CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, OR³,CH₂OR³, NR³R^(3a), CH₂NR³R^(3a), C(O)R³, CH₂C(O)R³, C(O)OR^(3c),CH₂C(O)OR^(3c), NR³C(O)R^(3a), CH₂NR³C(O)R^(3a), C(O)NR³R^(3a),CH₂C(O)NR³R^(3a), CF₃, CF₂CF₃, phenyl substituted with 0-2 R⁶, naphthylsubstituted with 0-2 R⁶, and benzyl substituted with 0-2 R⁶, providedthat R^(5a) does not form a S—N or S(O)_(p)—C(O) bond; and

R⁶, at each occurrence, is selected from H, OH, OR², F, Cl, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃,CN, NO₂, NR²R^(2a), CH₂NR²R^(2a), C(O)R^(2b), CH₂C(O)R^(2b),NR²C(O)R^(2b), NR²C(O)NR²R^(2a), C(═NH)NH₂, NHC(═NH)NH₂, SO₂NR²R^(2a),NR²SO₂NR²R^(2a), and NR²SO₂C₁₋₄ alkyl.

In a third embodiment, the present invention provides a novel compoundor a stereoisomer or pharmaceutically acceptable salt, solvate, orprodrug form thereof, wherein the compound is selected from:

P₄ is -G;

M₄ is -A-B;

G is substituted with 1 R^(a) and is selected from the following group,wherein R^(a) is attached adjacent to the point of attachment of G:

R^(a) is R^(b)(CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₁R^(c);

R^(b) is selected from C(O)NR³, S(O)₂NR³, NR³C(O), and NR³S(O)₂;

R^(c) is selected from H, OR³, NR³C(O)R³, C(O)NR³R^(3a), C₅₋₁₀carbocycle substituted with 0-2 R⁴, and 5-10 membered heterocyclesubstituted with 0-2 R⁴ and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p);

provided that when the (CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₁ portion ofR^(a) is absent, then R^(c) is selected from NR³C(O)R³, C₅₋₁₀ carbocyclesubstituted with 0-2 R⁴, and 5-10 membered heterocycle substituted with0-2 R⁴ and consisting of: carbon atoms and 1-4 heteroatoms selected fromthe group consisting of N, O, and S(O)_(p);

further provided that the (CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₄R^(c) portionof R^(a) is other than (CR⁸R^(2b))₀₋₃-unsubstituted-phenyl or(CR⁸R⁹)₀₋₃-unsubstituted-phenyl;

G₁ is absent or is selected from (CR³R^(3a))₁₋₃, CR³═CR³,(CR³R^(3a))_(u)C(O)(CR³R^(3a))_(w), (CR³R^(3a))_(u)O(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)C(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)C(O)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)C(O)(CR³R^(3a))_(u)C(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(CR³R^(3a))_(w), (CR³R^(3a))_(u)S(O)(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(O)₂(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)S(O)₂(CR³R^(3a))_(w), and(CR³R^(3a))_(u)S(O)₂NR^(3b)(CR³R^(3a))_(w), wherein u+w total 0, 1, or2, wherein the right side of G₁ is attached to ring G, provided that G₁does not form a N—S, NCH₂N, NCH₂O, or NCH₂S bond with either group towhich it is attached;

A is selected from one of the following carbocyclic and heterocyclicgroups which are substituted with 0-2 R⁴; cyclohexyl, phenyl,piperidinyl, piperazinyl, pyridyl, pyrimidyl, furanyl, morpholinyl,thienyl, pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl, thiazolyl,isothiazolyl, pyrazolyl, imidazolyl, 1,2,3-oxadiazolyl,1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl,1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl,1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl,1,3,4-triazolyl, benzofuranyl, benzothiofuranyl, indolinyl, indolyl,benzimidazolyl, benzoxazolyl, benzthiazolyl, indazolyl, benzisoxazolyl,benzisothiazolyl, and isoindazolyl;

B¹ is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, —(CH₂)₀₋₁—C₅₋₆carbocycle substituted with 0-2 R^(4b), and —(CH₂)₀₋₁-5-6 memberedheterocycle consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p) and substituted with 0-2R^(4b);

B² is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, C(O)R^(2e),C(O)NR^(2d)R^(2d), SO₂NR^(2d)R^(2d), and S(O)_(p)R^(5a);

B³ is selected from H, C₁₋₆ alkyl substituted with 0-1 R^(4c),—(CH₂)₀₋₁-3-6 membered carbocycle substituted with 0-1 R⁵, and a—(CH₂)₀₋₁-5-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-1 R⁵;

B⁴ is selected from H, SO₂R^(3b) and OR²;

B⁵ is NR²R^(2f);

ring Q is a 5-6 membered ring consisting of, in addition to theN—CR^(4d)═N group shown, carbon atoms and 0-2 heteroatoms selected fromN, O, and S(O)_(p), and the ring is substituted with an additional 0-2R^(4d);

Q⁴ is selected from C═O and SO₂;

ring Q³ is a 5-7 membered ring consisting of, in addition to the N-Q⁴group shown, carbon atoms and 0-2 heteroatoms selected from NR^(4c), O,S, S(O), and S(O)₂, wherein: 0-2 double bonds are present within thering and the ring is substituted with 0-2 R^(4a);

alternatively, ring Q³ is a 5-7 membered ring to which another ring isfused, wherein: the 5-7 membered ring consists of, in addition to theshown amide group, carbon atoms and 0-2 heteroatoms selected fromNR^(4c), O, S, S(O), and S(O)₂, and 0-1 double bonds are present withinthe ring; the fusion ring is phenyl or a 5-6 membered heteroaromaticconsisting of carbon atoms and 1-2 heteroatoms selected from NR^(4c), O,and S;

ring Q³, which includes the 5-7 membered ring and the fusion ring, issubstituted with 0-3 R^(4a);

ring Q⁵, is a C₃₋₆ monocyclic carbocycle or 5-6 membered monocyclicheterocycle, wherein the carobocycle or heterocycle consists of carbonatoms and 0-2 heteroatoms selected from N, O, and S(O)p, the carbocycleor heterocycle further comprises 0-1 double bonds and 0-1 carbonylgroups, and the carbocycle or heterocycle is substituted with 0-2 R⁴;

X is selected from —(CR²R^(2a))₁₋₂—, —C(═NR^(1b))—, —C(O)—, —S(O)₂—,—NR²S(O)₂—, —NR²S(O)₂—, —NR²C(O)—, —C(O)NR²—, —NR²C(O)CR²R^(2a)—,—NR²C(O)NR²—, NR², —NR²CR²R^(2a)—, —CR²R^(2a)NR²—, O, —OCR²R^(2a)—, and—CR²R^(2a)O—;

Y is selected from: CY¹Y²R^(4a), NR³R^(3a), and C(O)NR³R^(3a);

Y¹ and y are independently C₁₋₂ alkyl substituted with 0-2 R⁴;

alternatively, Y is selected from one of the following carbocyclic andheterocycles that are substituted with 1 R^(4a) and 0-1 R⁴: cyclopentyl,cyclohexyl, phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl,furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl,isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, oxadiazole,thiadiazole, triazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole,1,2,5-oxadiazole, 1,3,4-oxadiazole, 1,2,3-thiadiazole,1,2,4-thiadiazole, 1,2,5-thiadiazole, 1,3,4-thiadiazole, 1,2,3-triazole,1,2,4-triazole, 1,2,5-triazole, 1,3,4-triazole, benzofuran,benzothiofuran, indole, benzimidazole, benzimidazolone, benzoxazole,benzthiazole, indazole, benzisoxazole, benzisothiazole, and isoindazole;

R^(1a) is selected from H, R^(1b), CH(CH₃)R^(1b), C(CH₃)₂R^(1b),CH₂R^(1b), and CH₂CH₂R^(1b), provided that R^(1a) forms other than anN-halo, N—S, or N—CN bond;

alternatively, when two R^(1a) groups are attached to adjacent atoms,together with the atoms to which they are attached they form a 5-6membered ring consisting of: carbon atoms and 0-2 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), this ring beingsubstituted with 0-2 R^(4b) and 0-3 ring double bonds;

R^(1b) is selected from H, CH₃, CH₂CH₃, F, Cl, Br, —CN, —CHO, CF₃, OR²,NR²R^(2a), C(O)R^(2b), CO₂R^(2b), OC(O)R², CO₂R^(2a), S(O)_(p)R²,NR²(CH₂)_(r)OR², NR²C(O)R^(2b), C(O)NR²R^(2a), SO₂NR²R^(2a), NR²SO₂R²,phenyl substituted with 0-2 R^(4b), and 5-6 membered aromaticheterocycle consisting of carbon atoms and from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-2 R^(4b), provided that R^(1b) forms other than an O—O, N-halo, N—S,or N—CN bond;

R², at each occurrence, is selected from H, CF₃, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, phenyl substituted with 0-2 R^(4b), a benzyl substituted with0-2 R^(4b), and a 5-6 membered aromatic heterocycle consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p), and substituted with 0-2 R^(4b);

R^(2a), at each occurrence, is selected from H, CF₃, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, benzyl substituted with 0-2 R^(4b), phenylsubstituted with 0-2 R^(4b), and 5-6 membered aromatic heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p), and substituted with 0-2 R^(4b);

alternatively, NR²R^(2a) forms a 5 or 6 membered saturated, partiallysaturated or unsaturated ring substituted with 0-2 R^(4b) and consistingof: 0-1 additional heteroatoms selected from the group consisting of N,O, and S(O)_(p);

R^(2b), at each occurrence, is selected from CF₃, C₁₋₄ alkoxy, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzyl substituted with 0-2 R^(4b), phenylsubstituted with 0-2 R^(4b), and 5-6 membered aromatic heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p), and substituted with 0-2 R^(4b);

R^(2c), at each occurrence, is selected from CF₃, OH, OCH₃, OCH₂CH₃,OCH₂CH₂CH₃, OCH(CH₃)₂, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzylsubstituted with 0-2 R^(4b), phenyl substituted with 0-2 R^(4b), and 5-6membered aromatic heterocycle containing from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-2 R^(4b);

R^(2d), at each occurrence, is selected from H, R^(4c), C₁₋₄ alkylsubstituted with 0-2 R^(4c), C₃₋₆ carbocycle substituted with 0-2R^(4c), —(CR³R^(3a))—C₃₋₆ carbocycle substituted with 0-2 R^(4c), 5-6membered heterocycle substituted with 0-2 R^(4c) and consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p), and —(CR³R^(3a))-5-6 membered heterocyclesubstituted with 0-2 R^(4c) and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),provided that R^(2d) forms other than a N-halo, N—C-halo, S(O)_(p)-halo,O-halo, N—S, S—N, S(O)_(p)—S(O)_(p), S—O, O—N, O—S, or O—O moiety;

R^(2e), at each occurrence, is selected from H, R^(4c), C₁₋₄ alkylsubstituted with 0-2 R^(4c), C₃₋₆ carbocycle substituted with 0-2R^(4c), —(CR³R^(3a))—C₃₋₆ carbocycle substituted with 0-2 R^(4c), 5-6membered heterocycle substituted with 0-2 R^(4c) and consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p), and —(CR³R^(3a))-5-6 membered heterocyclesubstituted with 0-2 R^(4c) and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),provided that R^(2e) forms other than a C(O)-halo or C(O)—S(O)_(p)moiety;

R^(2f) at each occurrence, is selected from H, CF₃, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, OCH₃, and benzyl;

alternatively, NR²R^(2f) forms a 5-6 membered ring consisting of: carbonatoms and 0-2 additional heteroatoms selected from N, O, and S(O)_(p),and this ring is substituted with 0-2 R^(4b);

alternatively, B⁴ and R^(2f) combine to form a 5-6 membered ringconsisting of: carbon atoms and 0-1 additional heteroatoms selected fromN, O, and S(O)_(p), and this ring is substituted with 0-2 R^(4b) and theR² group of NR²R^(2f), in addition to the groups recited below, can beSO₂R^(3b);

R^(3b), at each occurrence, is selected from H, CF₃, CH₃, CH₂CH₃,CH₂CH₂CH₃, and CH(CH₃)₂;

R⁴, at each occurrence, is selected from H, ═O, CH₂OR², (CH₂)₂OR², OR²,F, Cl, Br, I, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, —CN, NO₂, NR²R^(2a), CH₂NR²R^(2a),(CH₂)₂NR²R^(2a), C(O)R^(2c), NR²C(O)R^(2b), C(O)NR²R^(2a),NR²C(O)NR²R^(2a), SO₂NR²R^(2a), CF₃, and CF₂CF₃;

R^(4a) is selected from —(CR³R^(3g))_(r)-5-6 membered carbocyclesubstituted with 0-3 R^(4c), —(CR³R^(3g))_(r)-5-6 membered heterocyclesubstituted with 0-3 R^(4c) and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),(CR³R^(3g))_(r)NR^(2d)R^(2d), (CR³R^(3g))_(r)N(→O)R^(2d)R^(2d),(CR³R^(3g))_(r)OR^(2d), (CR³R^(3g))_(r)—NR^(2d)C(O)R^(2e),(CR³R^(3g))_(r)—C(O)R^(2e), (CR³R^(3g))_(r)—OC(O)R^(2e),(CR³R^(3g))_(r)—C(O)NR^(2d)R^(2d), (CR³R^(3g))_(r)—C(O)OR^(2d),(CR³R^(3g))_(r)—NR^(2d)C(O)NR^(2d)R^(2d),(CR³R^(3g))_(r)—NR^(2d)C(O)OR^(2d), (CR³R^(3g))_(r)—SO₂NR^(2d)R^(2d),(CR³R^(3g))_(r)—NR^(2d)SO₂R^(2d), and (CR³R^(3g))_(r)—S(O)_(p)R^(2d),provided that S(O)_(p)R^(2d) forms other than S(O)₂H or S(O)H;

R^(4b), at each occurrence, is selected from H, ═O, OR³, CH₂OR³, F, Cl,CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, —CN, NO₂, NR³R^(3a), CH₂NR³R^(3a),C(O)R³, CH₂—C(O)R³, C(O)OR^(3c), CH₂—C(O)OR^(3c), NR³C(O)R^(3a),CH₂NR³C(O)R^(3a), C(O)NR³R^(3a), CH₂—C(O)NR³R^(3a), SO₂NR³R^(3a),CH₂SO₂NR³R^(3a), NR³SO₂—C₁₋₄ alkyl, CH₂NR³SO₂—C₁₋₄ alkyl, NR³SO₂-phenyl,CH₂NR³SO₂-phenyl, S(O)_(p)CF₃, CH₂S(O)_(p)CF₃, S(O)_(p)—C₁₋₄ alkyl,CH₂S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl, CH₂S(O)_(p)-phenyl, and CF₃;

R^(4c), at each occurrence, is selected from ═O, OR², (CR³R^(3a))OR², F,(CR³R^(3a))F, Br, (CR³R^(3a))Br, Cl, (CR³R^(3a))Cl, CF₃, (CR³R^(3a))CF₃,C₂₋₃ alkenyl, C₂₋₃ alkynyl, C₁₋₄ alkyl, —CN, (CR³R^(3a))CN, NO₂,(CR³R^(3a))NO₂, NR²R^(2a), (CR³R^(3a))NR²R^(2a), N(→O)R²R^(2a),(CR³R^(3a))N(O)R²R^(2a), C(O)R^(2c), (CR³R^(3a))C(O)R^(2c),NR²C(O)R^(2b), (CR³R^(3a))NR²C(O)R^(2b), C(O)NR²R^(2a),(CR³R^(3a))C(O)NR²R^(2a), NR²C(O)NR²R^(2a), (CR³R^(3a))NR²C(O)NR²R^(2a),SO₂NR²R^(2a), (CR³R^(3a))SO₂NR²R^(2a), NR²SO₂NR²R^(2a),(CR³R^(3a))NR²SO₂NR²R^(2a), NR²SO₂R^(5a), (CR³R^(3a))NR²SO₂R^(5a),S(O)_(p)R^(5a), (CR³R^(3a))S(O)_(p)R^(5a), CF₃, CF₂CF₃, C₃₋₁₀ carbocyclesubstituted with 0-2 R^(4b), (CR³R^(3a))C₃₋₁₀ carbocycle substitutedwith 0-2 R^(4b), 5-10 membered heterocycle consisting of carbon atomsand from 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p) and substituted with 0-2 R^(4b), and (CR³R^(3a))-5-10 memberedheterocycle consisting of carbon atoms and from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p) and substituted with 0-2R^(4b);

R^(4d), at each occurrence, is selected from H, CH₂OR², OR², CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃,C(CH₃)₃, —CN, NO₂, CH₂NR²R^(2a), NR²R^(2a), C(O)R^(2c), NR²C(O)R^(2b),C(O)NR²R^(2a), NR²C(O)NR²R^(2a), NR²SO₂R⁵, SO₂NR²R^(2a), 6-memberedcarbocycle substituted with 0-1 R⁵, and a 5-6 membered heterocycleconsisting of: carbon atoms and 1-2 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p) and substituted with 0-1 R⁵;

R⁵, at each occurrence, is selected from H, ═O, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, OR³, CH₂OR³, F, Cl, —CN, NO₂, NR³R^(3a), CH₂NR³R^(3a), C(O)R³,CH₂C(O)R³, C(O)OR^(3c), CH₂C(O)OR^(3c), NR³C(O)R^(3a), C(O)NR³R^(3a),SO₂NR³R^(3a), NR³SO₂—C₁₋₄ alkyl, NR³SO₂CF₃, NR³SO₂-phenyl, S(O)_(p)CF₃,S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl, CF₃, phenyl substituted with 0-2R⁶, naphthyl substituted with 0-2 R⁶, and benzyl substituted with 0-2R⁶; and

R⁶, at each occurrence, is selected from H, OH, OR², F, Cl, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, —CN, NO₂, NR²R^(2a), CH₂NR²R^(2a), C(O)R^(2b),CH₂C(O)R^(2b), NR²C(O)R^(2b), SO₂NR²R^(2a), and NR²SO₂C₁₋₄ alkyl.

In a fourth embodiment, the present invention provides a novel compoundor a stereoisomer or pharmaceutically acceptable salt, solvate, orprodrug form thereof, within the scope of the third embodiment, wherein:

G is substituted with 1 R^(a), wherein R^(a) is attached adjacent to thepoint of attachment of G:

R^(a) is R^(b)(CR⁸R^(2b))₀₋₃R^(b) ₀₋₁R^(c);

R^(b) is C(O)NR³;

R^(c) is selected from H, OR³, C₅₋₁₀ carbocycle substituted with 0-2 R⁴,and 5-10 membered heterocycle substituted with 0-2 R⁴ and consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p);

provided that when the (CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₁ portion ofR^(a) is absent, then R^(c) is selected from C₅₋₁₀ carbocyclesubstituted with 0-2 R⁴ and 5-11 membered heterocycle substituted with0-2 R⁴ and consisting of: carbon atoms and 1-4 heteroatoms selected fromthe group consisting of N, O, and S(O)_(p);

further provided that the (CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₄R^(c) portionof R^(a) is other than (CR⁸R^(2b))₀₋₃-unsubstituted-phenyl or(CR⁸R⁹)₀₋₃-unsubstituted-phenyl;

G₁ is absent or is selected from CH₂, CH₂CH₂, CH₂O, OCH₂, NH, CH₂NH,NHCH₂, CH₂C(O), C(O)CH₂, C(O)NH, NHC(O), CH₂S(O)₂, S(O)₂(CH₂), SO₂NH,and NHSO₂, wherein the right side of G₁ is attached to ring G, providedthat G₁ does not form a N—S, NCH₂N, NCH₂O, or NCH₂S bond with eithergroup to which it is attached;

A is selected from cyclohexyl, piperidinyl, piperazinyl, phenyl,pyridyl, and pyrimidyl, and is substituted with 0-2 R⁴;

B is selected from Y, N(B¹)C(O)C(R³R^(3g))NB²B³,

provided that Z and B are attached to different atoms on A, the R^(4d)shown is other than OH, and that the A-X—N moiety forms other than aN—N—N group;

B¹ is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, and CH(CH₃)₂;

B² is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, and CH(CH₃)₂;

B³ is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, C₂₋₅ alkyl substituted with 1R^(4c), —(CH₂)₀₋₁-3-6 membered carbocycle substituted with 0-1 R⁵, and a—(CH₂)₀₋₁-5-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-1 R⁵;

B⁴ is selected from H, SO₂R^(3b), and OR²;

B⁵ is NR²R^(2f);

ring Q is a 5-6 membered ring consisting of, in addition to theN—CR^(4d)═N group shown, carbon atoms and 0-1 heteroatoms selected fromN, O, and S(O)_(p), and the ring is substituted with an additional 0-2R^(4d);

Q⁴ is selected from C═O and SO₂;

ring Q³ is a 6-7 membered ring consisting of, in addition to the N-Q⁴group shown, carbon atoms and 0-1 heteroatoms selected from NR^(4c), O,S, S(O), and S(O)₂, wherein: 0-2 double bonds are present within thering and the ring is substituted with 0-2 R⁴;

alternatively, ring Q³ is a 5-7 membered ring to which another ring isfused, wherein: the 5-7 membered ring consists of, in addition to theshown amide group, carbon atoms and 0-1 heteroatoms selected fromNR^(4c), O, S, S(O), and S(O)₂, and 0-1 double bonds are present withinthe ring; the fusion ring is phenyl;

ring Q³, which includes the 5-7 membered ring and the fusion ring, issubstituted with 0-2 R⁴;

ring Q⁵ is substituted with 0-1 R⁴ and is selected from cyclopropyl,cyclobutyl, cyclopentyl, cyclopentanonyl, cyclohexyl, cyclohexanonyl,pyrrolidinyl, pyrrolidinonyl, piperidinyl, piperidinonyl,tetrahydrofuranyl, and tetrahydropyranyl;

X is selected from CH₂, C(O), —S(O)₂—, —NHC(O)—, —C(O)NH—, —CH₂NH—, O,and —CH₂O—;

Y is selected from N(CH₃)₂, C(O)(CH₃)₂, C(CH₃)₂R^(4a) andC(CH₂CH₃)₂R^(4a);

altneratively, Y is selected from phenyl, pyridyl, pyrrolidino,N-pyrrolidino-carbonyl, morpholino, N-morpholino-carbonyl,1,2,3-triazolyl, imidazolyl, and benzimidazolyl, and is substituted with1 R^(4a) and 0-1 R⁴;

R^(1a), at each occurrence, is selected from H, R^(1b), CH(CH₃)R^(1b),C(CH₃)₂R^(1b), and CH₂R^(1b), provided that R^(1a) forms other than anN-halo, N—S, or N—CN bond;

R^(1b) is selected from CH₃, CH₂CH₃, F, Cl, Br, —CN, CF₃, OR²,NR²R^(2a), C(O)R^(2b), CO₂R^(2b), CO₂R^(2a), S(O)_(p)R², C(O)NR²R^(2a),SO₂NR²R^(2a), NR²SO₂R², and 5-6 membered aromatic heterocycle consistingof carbon atoms and from 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p), and substituted with 0-2 R^(4b),provided that R^(1b) forms other than an O—O, N-halo, N—S, or N—CN bond;

R², at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, phenyl substituted with 0-1 R^(4b), benzyl substituted with0-1 R^(4b), and 5-6 membered aromatic heterocycle consisting of: carbonatoms and 1-4 heteroatoms selected from the group consisting of N, O,and S(O)_(p), and substituted with 0-1 R^(4b);

R^(2a), at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, benzyl substituted with 0-1 R^(4b), phenyl substituted with0-1 R^(4b), and 5-6 membered aromatic heterocycle consisting of: carbonatoms and 1-4 heteroatoms selected from the group consisting of N, O,and S(O)_(p), and substituted with 0-1 R^(4b);

alternatively, NR²R^(2a) forms a 5 or 6 membered saturated, partiallysaturated or unsaturated ring substituted with 0-1 R^(4b) and consistingof: 0-1 additional heteroatoms selected from the group consisting of N,O, and S(O)_(p);

R^(2b), at each occurrence, is selected from OCH₃, OCH₂CH₃, OCH₂CH₂CH₃,OCH(CH₃)₂, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzyl substituted with 0-1R^(4b), phenyl substituted with 0-1 R^(4b), and 5-6 membered aromaticheterocycle consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-1 R^(4b);

R^(2c), at each occurrence, is selected from OH, OCH₃, OCH₂CH₃,OCH₂CH₂CH₃, OCH(CH₃)₂, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzylsubstituted with 0-1 R^(4b), phenyl substituted with 0-1 R^(4b), and 5-6membered aromatic heterocycle containing from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-1 R^(4b);

R^(2d), at each occurrence, is selected from H, R^(4c), C₁₋₄ alkylsubstituted with 0-2 R^(4c), C₃₋₆ carbocycle substituted with 0-2R^(4c), —(CH₂)—C₃₋₆ carbocycle substituted with 0-2 R^(4c), 5-6 memberedheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), and —(CH₂)-5-6 membered heterocycle substituted with 0-2R^(4c) and consisting of: carbon atoms and 1-4 heteroatoms selected fromthe group consisting of N, O, and S(O)_(p), provided that R^(2d) formsother than a N-halo, N—C-halo, S(O)_(p)-halo, O-halo, N—S, S—N,S(O)_(p)—S(O)_(p), S—O, O—N, O—S, or O—O moiety;

R^(2e), at each occurrence, is selected from H, R^(4c), C₁₋₄ alkylsubstituted with 0-2 R^(4c), C₃₋₆ carbocycle substituted with 0-2R^(4c), —(CH₂)—C₃₋₆ carbocycle substituted with 0-2 R^(4c), 5-6 memberedheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), and —(CH₂)-5-6 membered heterocycle and consisting of: carbonatoms and 1-4 heteroatoms selected from the group consisting of N, O,and S(O)_(p), provided that R^(2e) forms other than a C(O)-halo orC(O)—S(O)_(p) moiety;

R^(2f), at each occurrence, is selected from H, CH₃, CH₂CH₃, OCH₃, andbenzyl;

alternatively, NR²R^(2f) forms a 5-6 membered ring consisting of: carbonatoms and 0-1 additional heteroatoms selected from N, O, and S(O)_(p),and this ring is substituted with 0-1 R^(4b);

alternatively, B⁴ and R^(2f) combine to form a 5 membered ringconsisting of: carbon atoms and 0-1 additional heteroatoms selected fromN, O, and S(O)_(p), and this ring is substituted with 0-2 R and the R²group of NR²R^(2f), in addition to the groups recited below, can beSO₂R^(3b);

R^(3b), at each occurrence, is selected from H and CH₃;

R⁴, at each occurrence, is selected from H, ═O, OH, OR², CH₂OR²,(CH₂)₂OR², F, Br, Cl, I, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, NR²R^(2a), CH₂NR²R^(2a),(CH₂)₂NR²R^(2a), C(O)R^(2c), NR²C(O)R^(2b), C(O)NR²R^(2a), SO₂NR²R^(2a),CF₃, and CF₂CF₃;

R^(4a) is selected from —(CR³R^(3g))_(r)-5-6 membered carbocyclesubstituted with 0-3 R^(4c), —(CR³R^(3g))_(r)-5-6 membered heterocyclesubstituted with 0-3 R^(4c) and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),(CR³R^(3g))_(r)NR^(2d)R^(2d), (CR³R^(3g))_(r)N(→O)R^(2d)R^(2d),(CR³R^(3g))_(r)OR^(2d), (CR³R^(3g))_(r)—C(O)NR^(2d)R^(2d),(CR³R^(3g))_(r)—NR^(2d)C(O)R^(2e), (CR³R^(3g))_(r)—C(O)R^(2e),(CR³R^(3g))_(r)—NR^(2d)C(O)NR^(2d)R^(2d),(CR³R^(3g))_(r)—NR^(2d)C(O)OR^(2d), (CR³R^(3g))_(r)—NR^(2d)SO₂R^(2d),and (CR³R^(3g))_(r)—S(O)_(p)R^(2d), provided that S(O)_(p)R^(2d) formsother than S(O)₂H or S(O)H;

R^(4b), at each occurrence, is selected from H, ═O, OR³, CH₂OR³, F, Cl,CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, —CN, NO₂, NR³R^(3a), CH₂NR³R^(3a),C(O)R³, C(O)OR^(3c), NR³C(O)R^(3a), C(O)NR³R^(3a), SO₂NR³R^(3a),NR³SO₂—C₁₋₄ alkyl, NR³SO₂-phenyl, S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl,and CF₃;

R^(4c), at each occurrence, is selected from ═O, OR², CH₂OR², F, Br, Cl,CF₃, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂,CH(CH₃)CH₂CH₃, C(CH₃)₃, C₂₋₃ alkenyl, C₂₋₃ alkynyl, —CN, NO₂, NR²R^(2a),CH₂NR²R^(2a), N(→O)R²R^(2a), CH₂N(→O)R²R^(2a), C(O)R^(2c),CH₂C(O)R^(2c), NR²C(O)R^(2b), CH₂NR²C(O)R^(2b), C(O)NR²R^(2a),CH₂C(O)NR²R^(2a), SO₂NR²R^(2a), CH₂SO₂NR²R^(2a), NR²SO₂R^(5a),CH₂NR²SO₂R^(5a), S(O)_(p)R^(5a), CH₂S(O)_(p)R^(5a), CF₃, CF₂CF₃, C₃₋₆carbocycle substituted with 0-2 R^(4b), (CH₂)C₃₋₆ carbocycle substitutedwith 0-2 R^(4b), 5-6 membered heterocycle consisting of carbon atoms andfrom 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p) and substituted with 0-2 R^(4b), and (CH₂)-5-6 memberedheterocycle consisting of carbon atoms and from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p) and substituted with 0-2R^(4b);

R^(4d), at each occurrence, is selected from H, CH₂OR², OR², CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃,C(CH₃)₃, CH₂NR²R^(2a), NR²R^(2a), C(O)R^(2c), NR²C(O)R^(2b),C(O)NR²R^(2a), SO₂NR²R^(2a), NR²SO₂R⁵, phenyl substituted with 0-1 R⁵,and a 5-6 membered heterocycle consisting of: carbon atoms and 1heteroatom selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-1 R⁵;

R⁵, at each occurrence, is selected from H, ═O, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, OR³, CH₂OR³, F, Cl, —CN, NO₂, NR³R^(3a), CH₂NR³R^(3a), C(O)R³,C(O)OR^(3c), NR³C(O)R^(3a), C(O)NR³R^(3a), SO₂NR³R^(3a), NR³SO₂—C₁₋₄alkyl, NR³SO₂-phenyl, S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl, CF₃, phenylsubstituted with 0-2 R⁶, naphthyl substituted with 0-2 R⁶, and benzylsubstituted with 0-2 R⁶; and

R⁶, at each occurrence, is selected from H, OH, OR², F, Cl, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, —CN, NO₂, NR²R^(2a), CH₂NR²R^(2a), C(O)R^(2b),CH₂C(O)R^(2b), NR²C(O)R^(2b), and SO₂NR²R^(2a).

In a fifth embodiment, the present invention provides a novel compoundor a stereoisomer or pharmaceutically acceptable salt, solvate, orprodrug form thereof, within the scope of the fourth embodiment,wherein:

A is selected from the group: cyclohexyl, phenyl, 2-pyridyl, 3-pyridyl,2-pyrimidyl, 2-Cl-phenyl, 3-Cl-phenyl, 2-F-phenyl, 3-F-phenyl,2-methylphenyl, 2-aminophenyl, and 2-methoxyphenyl;

B is selected from Y, N(B¹)C(O)C(R³R^(3g))NB²B³,

provided that Z and B are attached to different atoms on A and that theR^(4d) shown is other than OH;

B¹ is selected from H, CH₃, CH₂CH₃, and CH₂CH₂CH₃;

B² is selected from H, CH₃, and CH₂CH₃;

B³ is selected from CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,C(CH₃)₃, CH(CH₃)CH₂CH(CH₃)₂, CH₂CH₂OH, CH(CH₃)CH₂OH, CH(phenyl)CH₂CH₃,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and CH₂-cyclopropyl;

is attached to a different atom on A than M and is selected from thegroup:

ring Q⁵ is selected from cyclopropyl, cyclobutyl, cyclopentyl,2-cyclopentanonyl, cyclohexyl, 2-cyclohexanonyl, pyrrolidinyl (attachedto A and R^(4a) at the 2-position), pyrrolidinyl (attached to A andR^(4a) at the 3-position), 2-pyrrolidinonyl (attached to A and R^(4a) atthe 3-position), piperidinyl (attached to A and R^(4a) at the4-position), 4-piperdinonyl (attached to A and R^(4a) at the3-position), tetrahydrofuranyl, and tetrahydropyranyl (attached to A andR^(4a) at the 4-position);

Y is selected from N(CH₃)₂, C(O)(CH₃)₂, C(CH₃)₂R^(4a) andC(CH₂CH₃)₂R^(4a);

alternatively, Y is selected from phenyl, pyridyl, 1,2,3-triazolyl,imidazolyl, and benzimidazolyl, and is substituted with 1 R^(4a);

R^(1a), at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH₂F, CH₂Cl, Br, CH₂Br, —CN, CH₂CN, CF₃, CH₂CF₃, OCH₃, CH₂OH, C(CH₃)₂OH,CH₂OCH₃, NH₂, CH₂NH₂, NHCH₃, CH₂NHCH₃, N(CH₃)₂, CH₂N(CH₃)₂, CO₂H, COCH₃,CO₂CH₃, CH₂CO₂CH₃, SCH₃, CH₂SCH₃, S(O)CH₃, CH₂S(O)CH₃, S(O)₂CH₃,CH₂S(O)₂CH₃, C(O)NH₂, CH₂C(O)NH₂, SO₂NH₂, CH₂SO₂NH₂, NHSO₂CH₃,CH₂NHSO₂CH₃, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl,pyridin-2-yl-N-oxide, pyridin-3-yl-N-oxide, pyridin-4-yl-N-oxide,imidazol-1-yl, CH₂-imidazol-1-yl, 4-methyl-oxazol-2-yl,4-N,N-dimethylaminomethyl-oxazol-2-yl, 1,2,3,4-tetrazol-1-yl,1,2,3,4-tetrazol-5-yl, CH₂-1,2,3,4-tetrazol-1-yl, andCH₂-1,2,3,4-tetrazol-5-yl, provided that R^(1a) forms other than anN-halo, N—S, or N—CN bond;

R², at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, phenyl substituted with 0-1 R^(4b), benzyl substituted with0-1 R^(4b), and 5 membered aromatic heterocycle consisting of: carbonatoms and 1-4 heteroatoms selected from the group consisting of N, O,and S(O)_(p), and substituted with 0-1 R^(4b);

R^(2a), at each occurrence, is selected from H, CH₃, and CH₂CH₃;

alternatively, NR²R^(2a) forms a 5 or 6 membered saturated, partiallysaturated or unsaturated ring substituted with 0-1 R^(4b) and consistingof: 0-1 additional heteroatoms selected from the group consisting of N,O, and S(O)_(p);

R^(2b), at each occurrence, is selected from OCH₃, OCH₂CH₃, CH₃, andCH₂CH₃;

R^(2c), at each occurrence, is selected from OH, OCH₃, OCH₂CH₃, CH₃, andCH₂CH₃;

R^(2d), at each occurrence, is selected from H, R^(4c), C₁₋₄ alkylsubstituted with 0-2 R^(4c), C₃₋₆ cycloalkyl substituted with 0-2R^(4c), phenyl substituted with 0-2 R^(4c), and 5-6 membered aromaticheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), provided that R^(2d) forms other than a N-halo, N—C-halo,S(O)_(p)-halo, O-halo, N—S, S—N, S(O)_(p)—S(O)_(p), S—O, O—N, O—S, orO—O moiety;

R^(2e), at each occurrence, is selected from H, R^(4c), C₁₋₄ alkylsubstituted with 0-2 R^(4c), C₃₋₆ cycloalkyl substituted with 0-2R^(4c), phenyl substituted with 0-2 R^(4c), and 5-6 membered aromaticheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), provided that R^(2e) forms other than a C(O)-halo orC(O)—S(O)_(p) moiety;

R^(2f), at each occurrence, is selected from H, CH₃, CH₂CH₃, and OCH₃;

alternatively, NR²R^(2f) forms a ring selected from morpholine,piperazine, piperidine, and pyrrolidine;

R⁴, at each occurrence, is selected from H, ═O, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, and C(CH₃)₃;

R^(4a) is selected from —(CH₂)_(r)-5-6 membered carbocycle substitutedwith 0-3 R^(4c), —(CH₂)_(r)-5-6 membered heterocycle substituted with0-3 R^(4c) and consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), (CH₂)_(r)NR^(2d)R^(2d),(CH₂)_(r)N(→O)R^(2d)R^(2d), (CH₂)_(r)OR^(2d),(CH₂)_(r)—C(O)NR^(2d)R^(2d), (CH₂)_(r)—NR^(2d)C(O)R^(2e),(CH₂)_(r)—C(O)R^(2e), (CH₂)_(r)—NR^(2d)C(O)NR^(2d)R^(2d),(CH₂)_(r)—NR^(2d)C(O)OR^(2d), (CH₂)_(r)—NR^(2d)SO₂R^(2d), and(CH₂)_(r)—S(O)_(p)R^(2d), provided that S(O)_(p)R^(2d) forms other thanS(O)₂H or S(O)H;

R^(4b), at each occurrence, is selected from H, ═O, OR³, CH₂OR³, F, Cl,CH₃, CH₂CH₃, NR³R^(3a), CH₂NR³R^(3a), C(O)R³, C(O)OR^(3c),NR³C(O)R^(3a), C(O)NR³R^(3a), SO₂NR³R^(3a), NR³SO₂-phenyl, S(O)₂CH₃,S(O)₂-phenyl, and CF₃;

R^(4c), at each occurrence, is selected from ═O, OH, OCH₃, OCH₂CH₃,OCH₂CH₂CH₃, OCH(CH₃)₂, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, C₂₋₃ alkenyl,C₂₋₃ alkynyl, CH₂OH, CH₂OCH₃, CH₂OCH₂CH₃, CH₂OCH₂CH₂CH₃, CH₂OCH(CH₃)₂,F, Br, Cl, CF₃, NR²R^(2a), CH₂NR²R^(2a), N(→O)R²R^(2a),CH₂N(→O)R²R^(2a), C(O)R^(2c), CH₂C(O)R^(2c), NR²C(O)R^(2b),CH₂NR²C(O)R^(2b), C(O)NR²R^(2a), CH₂C(O)NR²R^(2a), SO₂NR²R^(2a),CH₂SO₂NR²R^(2a), NR²SO₂R^(5a), CH₂NR²SO₂R^(5a), S(O)_(p)R^(5a),CH₂S(O)_(p)R^(5a), CF₃, cyclopropyl substituted with 0-1 R^(4b),cyclobutyl substituted with 0-1 R^(4b), cyclopentyl substituted with 0-1R^(4b), phenyl substituted with 0-1 R^(4b), —CH₂-cyclopropyl substitutedwith 0-1 R^(4b), —CH₂-cyclobutyl substituted with 0-1 R^(4b),—CH₂-cyclopentyl substituted with 0-1 R^(4b), benzyl substituted with0-2 R^(4b), 5-6 membered aromatic heterocycle consisting of carbon atomsand from 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p) and substituted with 0-2 R^(4b), and (CH₂)-5-6 memberedaromatic heterocycle consisting of carbon atoms and from 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p) and substitutedwith 0-2 R^(4b);

R^(4d), at each occurrence, is selected from H, OCH₃, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, NR²R^(2a), NR²C(O)R^(2b), NR²SO₂R⁵, phenyl,2-oxo-pyrrolidinyl, and 2-oxo-piperidinyl;

R⁵, at each occurrence, is selected from H, ═O, CH₃, CH₂CH₃, OR³,CH₂OR³, F, Cl, NR³R^(3a), CH₂NR³R^(3a), C(O)R³, C(O)OR^(3c),NR³C(O)R^(3a), C(O)NR³R^(3a), SO₂NR³R^(3a), NR³SO₂—C₁₋₄ alkyl,NR³SO₂-phenyl, S(O)₂—CH₃, S(O)₂-phenyl, CF₃, phenyl substituted with 0-2R⁶, naphthyl substituted with 0-2 R⁶, and benzyl substituted with 0-2R⁶; and

R⁶, at each occurrence, is selected from H, OH, OR², F, Cl, CH₃, CH₂CH₃,NR²R^(2a), CH₂NR²R^(2a), C(O)R^(2b), CH₂C(O)R^(2b), NR²C(O)R^(2b), andSO₂NR²R^(2a).

In a sixth embodiment, the present invention provides a novel compoundor a stereoisomer or pharmaceutically acceptable salt, solvate, orprodrug form thereof, within the scope of the fourth embodiment,wherein:

A is selected from the group: phenyl, 2-pyridyl, 2-pyrimidyl, and2-F-phenyl, wherein B is substituted at the 4-position of A;

B is selected from:

R^(2d), at each occurrence, is selected from H, C₁₋₄ alkyl substitutedwith 0-1 R^(4c), C₃₋₆ cycloalkyl substituted with 0-2 R^(4c), phenylsubstituted with 0-2 R^(4c), and a 5-6 membered aromatic heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p), provided that R^(2d) forms other thana N-halo, N—C-halo, S(O)_(p)-halo, O-halo, N—S, S—N, S(O)_(p)—S(O)_(p),S—O, O—N, O—S, or O—O moiety;

R^(2e), at each occurrence, is selected from H, C₁₋₄ alkyl substitutedwith 0-1 R^(4c), C₃₋₆ cycloalkyl substituted with 0-2 R^(4c), phenyl,substituted with 0-2 R^(4c), and 5-6 membered aromatic heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p), provided that R^(2e) forms other thana C(O)-halo or C(O)—S(O)_(p) moiety;

R^(4a) is selected from NR^(2d)R^(2d), CH₂NR^(2d)R^(2d),CH₂CH₂NR^(2d)R^(2d), N(→O)R^(2d)R^(2d), CH₂N(→O)R^(2d)R^(2d),CH₂OR^(2d), C(O)R^(2e), C(O)NR^(2d)R^(2d), CH₂C(O)NR^(2d)R^(2d),NR^(2d)C(O)R^(2e), CH₂NR^(2d)C(O)R^(2e), NR^(2d)C(O)NR^(2d)R^(2d),CH₂NR^(2d)C(O)NR^(2d)R^(2d), NR^(2d)C(O)OR^(2d), CH₂NR^(2d)C(O)OR^(2d),NR^(2d)SO₂R^(2d), CH₂NR^(2d)SO₂R^(2d), S(O)_(p)R^(2d),CH₂S(O)_(p)R^(2d), 5-6 membered carbocycle substituted with 0-2 R^(4c),—(CH₂)-5-6 membered carbocycle substituted with 0-2 R^(4c), 5-6 memberedheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), and —(CH₂)-5-6 membered heterocycle substituted with 0-2R^(4c) and consisting of: carbon atoms and 1-4 heteroatoms selected fromthe group consisting of N, O, and S(O)_(p) provided that S(O)_(p)R^(2d)forms other than S(O)₂H or S(O)H; and

R^(4c) is selected from ═O, OH, OCH₃, OCH₂CH₃, OCH₂CH₂CH₃, OCH(CH₃)₂,CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH═CH₂, CH≡CH, CH₂OH, CH₂OCH₃,CH₂OCH₂CH₃, CH₂OCH₂CH₂CH₃, CH₂OCH(CH₃)₂, F, Br, Cl, CF₃, NR²R^(2a),CH₂NR²R^(2a), C(O)R^(2c), CH₂C(O)R^(2c), NR²C(O)R^(2b),CH₂NR²C(O)R^(2b), C(O)NR²R^(2a), CH₂C(O)NR²R^(2a), SO₂NR²R^(2a),CH₂SO₂NR²R^(2a), NR²SO₂R^(5a), CH₂NR²SO₂R^(5a), S(O)_(p)R^(5a), andCH₂S(O)_(p)R^(5a).

In a seventh embodiment, the present invention provides a novel compoundof

or a stereoisomer or pharmaceutically acceptable salt, solvate, orprodrug form thereof, wherein:

P₄ is -G;

M₄ is -A-B;

A-B is selected from:

R^(2d), at each occurrence, is selected from H, Cl₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH(CH₃)₂, CH₂CH₂CH(CH₃)₂, CH₂CCH, CH₂CH₂OH, CH₂C(O)NH₂,cyclopropyl, CH₂-cyclopropyl, cyclobutyl, cyclopentyl, and thiazolyl;

R^(2e), at each occurrence, is selected from CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH(CH₃)₂, CH₂CH₂CH(CH₃)₂, CH₂-cyclopropyl, cyclopropyl, andcyclopentyl;

R^(4a) is substituted with 0-2 R^(4c) and selected from morpholine,1,1-dioxo-thiomorpholine, dihydropyridine, piperidine, piperazine,pyrrolidine, imidazole, imidazoline, imidazolidine, oxazoline, andthiazoline; and

R^(4c) is selected from ═O, OH, OCH₃, and CH₃.

In an eighth embodiment, the present invention provides a novel compoundor a stereoisomer or pharmaceutically acceptable salt, solvate, orprodrug form thereof, wherein the compound is selected from the group:Examples 3-30, 32-33, 37-44, 61, 109-118, 135-146, 148-151, 154-165,168-192, 195-199, 204-205, 207-213, 215, 217, 219-232, 235-237, 240-241,and, 244-255.

In a ninth embodiment, the present invention provides a novel compound,wherein the compound is of Formula IIIa, IIIb, or IIIc:

or a stereoisomer or pharmaceutically acceptable salt, solvate, orprodrug form thereof, wherein;

ring M, including M₁, M₂, and, if present, M₃, is phenyl or a 3-10membered carbocyclic or 4-10 membered heterocyclic ring consisting of:carbon atoms and 1-4 heteroatoms selected from O, S(O)_(p), N, and NZ²;

ring M is substituted with 0-3 R^(1a) and 0-2 carbonyl groups, and thereare 0-3 ring double bonds;

one of P₄ and M₄ is -Z-A-B and the other -G₁-G;

G is a group of Formula IIa or IIb:

in formula IIa, ring E is substituted with 1-2 R^(a), provided that atleast one R^(a) is ortho to the point of attachment of ring E;

in formula IIb, ring D is substituted with 1-2 R^(a), provided that atleast one R^(a) is ortho to the point of attachment of ring D;

ring D, including the two atoms of Ring E to which it is attached, is a5-6 membered ring consisting of: carbon atoms and 0-2 heteroatomsselected from the group consisting of N, O, and S(O)_(p);

ring D is substituted with 0-2 R and there are 0-3 ring double bonds;

E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, andpyridazinyl, and is substituted with 0-2 R;

alternatively, ring D is absent, and ring E is selected from phenyl,pyridyl, pyrimidyl, and thienyl, and ring E is substituted with 0-2 R;

alternatively, ring D is absent, ring E is selected from phenyl,pyridyl, and thienyl, and ring E is substituted with 0-2 R and a 5-6membered heterocycle consisting of: carbon atoms and 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p), wherein the5-6 membered heterocycle is substituted with 0-2 carbonyl and 1-2 R andthere are 0-3 ring double bonds;

R is selected from H, C₁₋₄ alkyl, F, Cl, OH, OCH₃, OCH₂CH₃, OCH(CH₃)₂,CN, C(═NH)NH₂, C(═NH)NHOH, C(═NH)NHOCH₃, NH₂, NH(C₁₋₃ alkyl), N(C₁₋₃alkyl)₂, C(═NH)NH₂, CH₂NH₂, CH₂NH(C₁₋₃ alkyl), CH₂N(C₁₋₃ alkyl)₂,(CR⁸R⁹)_(t)NR⁷R⁸, C(O)NR⁷R⁸, CH₂C(O)NR⁷R⁸, S(O)_(p)NR⁷R⁸,CH₂S(O)_(p)NR⁷R⁸, SO₂R³, and OCF₃;

alternatively, when 2 R groups are attached to adjacent atoms, theycombine to form methylenedioxy or ethylenedioxy;

R^(a) is (CR⁸R⁹)₀₋₁R^(b)(CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₁R^(c);

R^(b) is selected from O, C(O), C(O)NR³, C(O)N((CH₂)₂₋₃R³), S(O), S(O)₂,S(O)₂NR³, NR³, NR³C(O), and NR³S(O)₂;

R^(c) is selected from H, OR³, NR³C(O)R³, C(O)R³, CO₂R³, C(O)NR³R^(3a),S(O)₂NR³R^(3a), —CN, C₃₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-12membered heterocycle substituted with 0-2 R⁴ and consisting of: carbonatoms and 1-4 heteroatoms selected from the group consisting of N, O,and S(O)_(p);

R^(c) is selected from H, OR³, NR³C(O)R³, C(O)R³, CO₂R³, C(O)NR³R^(3a),S(O)₂NR³R^(3a), C₅₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-10membered heterocycle substituted with 0-2 R⁴ and consisting of: carbonatoms and 1-4 heteroatoms selected from the group consisting of N, O,and S(O)_(p);

provided that when the (CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₁ portion ofR^(a) is absent, then R^(c) is selected from NR³C(O)R³, S(O)₂NR³R^(3a),C₅₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-10 membered heterocyclesubstituted with 0-2 R⁴ and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p);

further provided that when the R^(a) is C(O)—NR*R* and NR*R* is aheterocyclic ring, then the heterocyclic ring is substituted with 1-2R⁴;

further provided that the (CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₄R^(c) portionof R^(a) is other than (CR⁸R^(2b))₀₋₃-unsubstituted-phenyl or(CR⁸R⁹)₀₋₃-unsubstituted-phenyl;

A is selected from: C₅₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-10membered heterocycle consisting of: carbon atoms and 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p) and substitutedwith 0-2 R⁴;

B is selected from Y, X—Y, N(B¹)C(O)C(R³R^(3g))NB²B³,N(B¹)C(O)C(R³R^(3g))C(R³R^(3g))NB²B³,

provided that Z and B are attached to different atoms on A, the R^(4d)shown is other than OH, and that the A-X—N moiety forms other than aN—N—N group;

B¹ is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, —(CH₂)₀₋₁—C₃₋₇ carbocyclesubstituted with 0-2 R^(4b), and —(CH₂)₀₋₁-5-6 membered heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p) and substituted with 0-2 R^(4b);

B² is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, NR^(2d)R^(2d), CH₂—NR^(2d)R^(2d),CH₂CH₂—NR^(2d)R^(2d), C(O)R^(2e), C(O)NR^(2d)R^(2d), SO₂NR^(2d)R^(2d),and S(O)_(p)R^(5a);

B³ is selected from H, C₁₋₆ alkyl substituted with 0-1 R^(4c),—(CH₂)₀₋₁-3-6 membered carbocycle substituted with 0-1 R⁵, and a—(CH₂)₀₋₁-5-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-1 R⁵;

B⁴ is selected from H, SO₂R^(3b), C(O)R^(3b), SO₂NR³R^(3b),C(O)NR³R^(3b), OR², and —CN;

B⁵ is NR²R^(2f) or CR³R²R^(2f);

ring Q is a 5-6 membered ring consisting of, in addition to theQ¹-CR^(4d)=Q² group shown, carbon atoms and 0-2 heteroatoms selectedfrom N, O, and S(O)_(p), and the ring is substituted with an additional0-2 R^(4d);

Q¹ and Q² are each N;

alternatively, Q¹ is CR³ and R^(4d) is NR²R^(2a) or NR^(3a)B⁴, providedthat when Q¹ is CR³, then this R³ group optionally forms a ring with theR² group of R^(4d), this ring is a 5-6 membered ring consisting of, inaddition to the C—C—N shown, carbon atoms and from 0-1 additionalheteroatoms selected from N, O, and S(O)_(p), and this ring issubstituted with 0-1 R⁵;

Q⁴ is selected from C═O and SO₂;

ring Q³ is a 4-7 membered monocyclic or tricyclic ring consisting of, inaddition to the N-Q⁴ group shown, carbon atoms and 0-2 heteroatomsselected from NR^(4c), O, S, S(O), and S(O)₂, wherein: 0-2 double bondsare present within the ring and the ring is substituted with 0-2 R⁴;

alternatively, ring Q³ is a 4-7 membered ring to which another ring isfused, wherein: the 4-7 membered ring consists of, in addition to theshown amide group, carbon atoms and 0-2 heteroatoms selected fromNR^(4c), O, S, S(O), and S(O)₂ and 0-1 double bonds are present withinthe ring; the fusion ring is phenyl or a 5-6 membered heteroaromaticconsisting of carbon atoms and 1-2 heteroatoms selected from NR^(4c), O,and S;

ring Q³, which includes the 4-7 membered ring and the fusion ring, issubstituted with 0-3 R⁴;

ring Q⁵ is a C₃₋₇ monocyclic carbocycle or 3-7 membered monocyclicheterocycle, wherein the carbocycle or heterocycle consists of: carbonatoms and 0-2 heteroatoms selected from N, O, and S(O)_(p), thecarbocycle or heterocycle further comprises 0-2 double bonds and 0-2carbonyl groups, and the carbocycle or heterocycle is substituted with0-2 R⁴;

X is selected from —(CR²R^(2a))₁₋₄—, —C(O)—, C(═NR^(1c))—,—CR²(NR^(1b)R²)—, —C(O)CR²R^(2a)—, —CR²R^(2a)C(O), —C(O)NR²—, —NR²C(O)—,—C(O)NR²CR²R^(2a)—, —NR²C(O)CR²R^(2a)—, —CR²R^(2a)C(O)NR²—,—CR²R^(2a)NR²C(O)—, —NR²C(O)NR²—, —NR²—, —NR²CR²R^(2a)—, —CR²R^(2a)NR²—,—S(O)₂—, —NR²S(O)₂—, O, —CR²R^(2a)O—, and —OCR²R^(2a)—;

Y is selected from: CY¹Y²R^(4a), NR³R^(3a), and C(O)NR³R^(3a);

Y¹ and Y² are independently C₁₋₃ alkyl substituted with 0-2 R⁴;

alternatively, Y is selected from one of the following carbocyclic andheterocycles that are substituted with 1 R^(4a) and 0-2 R⁴: cyclopropyl,cyclopentyl, cyclohexyl, phenyl, piperidinyl, piperazinyl, pyridyl,pyrimidyl, furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl,oxazolyl, isoxazolyl, isoxazolinyl, thiazolyl, isothiazolyl, pyrazolyl,imidazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl,1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl,1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl,1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, benzofuranyl,benzothiofuranyl, indolyl, benzimidazolyl, benzoxazolyl, benzthiazolyl,indazolyl, benzisoxazolyl, benzisothiazolyl, and isoindazolyl;

Z is selected from a bond, CH₂, CH₂CH₂, CH₂O, OCH₂, C(O), NH, CH₂NH,NHCH₂, CH₂C(O), C(O)CH₂, C(O)NH, NHC(O), NHC(O)CH₂C(O)NH, S(O)₂,CH₂S(O)₂, S(O)₂(CH₂), SO₂NH, and NHSO₂, wherein the right side of Z isattached to ring A, provided that Z does not form a N—S, NCH₂N, NCH₂O,or NCH₂S bond with either group to which it is attached;

Z² is selected from H, C₁₋₄ alkyl, phenyl, benzyl, C(O)R^(3b),S(O)R^(3f), and S(O)₂R^(3f);

R^(1a), at each occurrence, is selected from H, —(CH₂)_(r)—R^(1b),—(CH(CH₃))_(r)—R^(1b), —(C(CH₃)₂)_(r)—R^(1b), —O—(CR³R^(3a))_(r)—R^(1b),—NR²—(CR³R^(3a))_(r)—R^(1b), and —S—(CR³R^(3a))_(r)—R^(1b), providedthat R^(1a) forms other than an N-halo, N—S, O—O, or N—CN bond;

alternatively, when two R^(1a) groups are attached to adjacent atoms,together with the atoms to which they are attached they form a 5-7membered ring consisting of: carbon atoms and 0-2 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), this ring beingsubstituted with 0-2 R^(4b) and 0-3 ring double bonds;

R^(1b) is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, F, Cl, Br,I, —CN, —CHO, CF₃, OR², NR²R^(2a), C(O)R^(2b), CO₂R^(2b), OC(O)R²,CO₂R^(2a), S(O)_(p)R², NR²(CH₂)_(r)OR², NR²C(O)R^(2b), NR²C(O)NHR²,NR²C(O)₂R^(2a), OC(O)NR²R^(2a), C(O)NR²R^(2a), C(O)NR²(CH₂)_(r)OR²,SO₂NR²R^(2a), NR²SO₂R², C₅₋₆ carbocycle substituted with 0-2 R^(4b), and5-6 membered heterocycle consisting of carbon atoms and from 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),and substituted with 0-2 R^(4b), provided that R^(1b) forms other thanan O—O, N-halo, N—S, or N—CN bond;

R², at each occurrence, is selected from H, CF₃, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, benzylsubstituted with 0-2 R^(4b), C₅₋₆ carbocycle substituted with 0-2R^(4b), a C₅₋₆ carbocyclic-CH₂-group substituted with 0-2 R^(4b), and5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p), andsubstituted with 0-2 R^(4b);

R^(2a), at each occurrence, is selected from H, CF₃, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃,benzyl substituted with 0-2 R^(4b), C₅₋₆ carbocycle substituted with 0-2R^(4b), and 5-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),and substituted with 0-2 R^(4b);

alternatively, NR²R^(2a) forms a 5 or 6 membered saturated, partiallysaturated or unsaturated ring substituted with 0-2 R^(4b) and consistingof: 0-1 additional heteroatoms selected from the group consisting of N,O, and S(O)_(p);

R^(2b), at each occurrence, is selected from CF₃, C₁₋₄ alkoxy, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃,C(CH₃)₃, benzyl substituted with 0-2 R^(4b), C₅₋₆ carbocycle substitutedwith 0-2 R^(4b), and 5-6 membered heterocycle consisting of: carbonatoms and 1-4 heteroatoms selected from the group consisting of N, O,and S(O)_(p), and substituted with 0-2 R^(4b);

R^(2c), at each occurrence, is selected from CF₃, OH, C₁₋₄ alkoxy, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃,C(CH₃)₃, benzyl substituted with 0-2 R^(4b), C₅₋₆ carbocycle substitutedwith 0-2 R^(4b), and 5-6 membered heterocycle containing from 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),and substituted with 0-2 R^(4b);

R^(2d), at each occurrence, is selected from H, R^(4c), C₁₋₄ alkylsubstituted with 0-2 R^(4c), —(CR³R^(3a))_(r)—C₃₋₆ carbocyclesubstituted with 0-2 R^(4c), and —(CR³R^(3a))_(r)-5-6 memberedheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), provided that R^(2d) forms other than a N-halo, N—C-halo,S(O)_(p)-halo, O-halo, N—S, S—N, S(O)_(p)—S(O)_(p), S—O, O—N, O—S, orO—O moiety;

alternatively, NR^(2d)R^(2d) forms a 5 or 6 membered saturated,partially saturated or unsaturated ring substituted with 0-2 R^(4b) andconsisting of: 0-1 additional heteroatoms selected from the groupconsisting of N, O, and S(O)_(p);

R^(2e), at each occurrence, is selected from H, R^(4c), C₁₋₄ alkylsubstituted with 0-2 R^(4c), —(CR³R^(3a))_(r)—C₃₋₆ carbocyclesubstituted with 0-2 R^(4c), and —(CR³R^(3a))_(r)-5-6 memberedheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), provided that R^(2e) forms other than a C(O)-halo orC(O)—S(O)_(p) moiety;

R^(2f), at each occurrence, is selected from H, CF₃, C₁₋₄ alkoxy, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃,C(CH₃)₃, benzyl substituted with 0-1 R^(4b), C₅₋₆ carbocycle substitutedwith 0-2 R^(4b), and 5-6 membered heterocycle containing from 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-2 R^(4b);

alternatively, CR²R^(2f) forms a 5-6 membered ring consisting of: carbonatoms and 0-2 heteroatoms selected from N, O, and S(O)_(p), and thisring is substituted with 0-2 R^(4b);

alternatively, NR²R^(2f) forms a 5-6 membered ring consisting of: carbonatoms and 0-2 additional heteroatoms selected from N, O, and S(O)_(p),and this ring is substituted with 0-2 R^(4b);

alternatively, when B⁵ is NR²R^(2f), B⁴ and R^(2f) combine to form a 5-6membered ring consisting of: carbon atoms and 0-2 additional heteroatomsselected from N, O, and S(O)_(p), and this ring is substituted with 0-2R^(4b) and the R² group of NR²R^(2f), in addition to the groups recitedbelow, is selected from SO₂R^(3b) and C(O)R^(3b);

R³, at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, benzyl, and phenyl;

R^(3a), at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, benzyl, and phenyl;

alternatively, R³ and R^(3a), together with the nitrogen atom to whichthey are attached, combine to form a 5 or 6 membered saturated,partially unsaturated, or unsaturated ring consisting of: carbon atomsand the nitrogen atom to which R³ and R^(3a) are attached;

R^(3b), at each occurrence, is selected from H, CF₃, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, —(C₀₋₁ alkyl)-5-6 membered carbocycle substitutedwith 0-1 R^(1a), and —(C₀₋₁ alkyl)-5-6 membered heterocycle substitutedwith 0-1 R^(1a) and consisting of: carbon atoms and 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p);

R^(3c), at each occurrence, is selected from CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, benzyl, and phenyl;

R^(3d), at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂-phenyl, CH₂CH₂-phenyl, and C(═O)R^(3c);

R⁴, at each occurrence, is selected from ═O, OR², CH₂OR², (CH₂)₂OR², F,Cl, Br, I, C₁₋₄ alkyl, —CN, NO₂, NR²R^(2a), CH₂NR²R^(2a),(CH₂)₂NR²R^(2a), C(O)R^(2c), NR²C(O)R^(2b), C(O)NR²R^(2a),NR²C(O)NR²R^(2a), SO₂NR²R^(2a), NR²SO₂NR²R^(2a), S(O)_(p)R^(5a),NR²SO₂—C₁₋₄ alkyl, NR²SO₂R⁵, CF₃, CF₂CF₃, 5-6 membered carbocyclesubstituted with 0-1 R⁵, and a 5-6 membered heterocycle consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p), and substituted with 0-1 R⁵;

R^(4b), at each occurrence, is selected from H, ═O, OR³, CH₂OR³, F, Cl,CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂,CH(CH₃)CH₂CH₃, C(CH₃)₃, —CN, NO₂, NR³R^(3a), CH₂NR³R^(3a), C(O)R³,CH₂—C(O)R³, C(O)OR^(3c), CH₂C(O)OR^(3c), NR³C(O)R^(3a),CH₂NR³C(O)R^(3a), C(O)NR³R^(3a), CH₂C(O)NR³R^(3a), NR³C(O)NR³R^(3a),CH₂NR³C(O)NR³R^(3a), C(═NR³)NR³R^(3a), CH₂C(═NR³)NR³R^(3a),NR³C(═NR³)NR³R^(3a), CH₂NR³C(═NR³)NR³R^(3a), SO₂NR³R^(3a),CH₂SO₂NR³R^(3a), NR³SO₂NR³R^(3a), CH₂NR³SO₂NR³R^(3a), NR³SO₂—C₁₋₄ alkyl,CH₂NR³SO₂—C₁₋₄ alkyl, NR³SO₂CF₃, CH₂NR³SO₂CF₃, NR³SO₂-phenyl,CH₂NR³SO₂-phenyl, S(O)_(p)CF₃, CH₂S(O)_(p)CF₃, S(O)_(p)—C₁₋₄ alkyl,CH₂S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl, CH₂S(O)_(p)-phenyl, CF₃, andCH₂—CF₃;

R^(4c), at each occurrence, is selected from ═O, (CR³R^(3a))_(r)OR²,(CR³R^(3a))_(r)F, (CR³R^(3a))_(r)Br, (CR³R^(3a))_(r)Cl,(CR³R^(3a))_(r)CF₃, C₁₋₄ alkyl, C₂₋₃ alkenyl, C₂₋₃ alkynyl,(CR³R^(3a))_(r)CN, (CR³R^(3a))_(r)NO₂, (CR³R^(3a))_(r)NR²R^(2a),(CR³R^(3a))_(r)N(→O)R²R^(2a), (CR³R^(3a))_(r)C(O)R^(2c),(CR³R^(3a))_(r)NR²C(O)R^(2b), (CR³R^(3a))_(r)C(O)NR²R^(2a),(CR³R^(3a))_(r)NR²C(O)NR²R^(2a), (CR³R^(3a))_(r)SO₂NR²R^(2a),(CR³R^(3a))_(r)NR²SO₂NR²R^(2a), (CR³R^(3a))_(r)NR²SO₂R^(5a),(CR³R^(3a))_(r)C(O)NR²SO₂R^(5a), (CR³R^(3a))_(r)S(O)_(p)R^(5a),(CF₂)_(r)CF₃, (CR³R^(3a))_(r)C₃₋₁₀ carbocycle substituted with 0-2R^(4b), and (CR³R^(3a))_(r)5-10 membered heterocycle consisting ofcarbon atoms and from 1-4 heteroatoms selected from the group consistingof N, O, and S(O)_(p) and substituted with 0-2 R^(4b);

R^(4d), at each occurrence, is selected from H, CH₂OR², OR², C₁₋₄ alkyl,CH₂—CN, —CN, CH₂NO₂, NO₂, CH₂NR²R^(2a), NR²R^(2a), CH₂—C(O)R^(2c),C(O)R^(2c), NR²C(O)R^(2b), (CH₂)_(r)C(O)NR²R^(2a), NR²C(O)NR²R^(2a),(CH₂)_(r)SO₂NR²R^(2a), NR²SO₂NR²R^(2a), NR²SO₂R⁵,(CH₂)_(r)S(O)_(p)R^(5a), CH₂CF₃, CF₃, CH₂-5-6 membered carbocyclesubstituted with 0-1 R⁵, 5-6 membered carbocycle substituted with 0-1R⁵, a CH₂-5-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-1 R⁵, and a 5-6 membered heterocycle consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p) and substituted with 0-1 R⁵;

R⁵, at each occurrence, is selected from H, ═O, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, OR³,CH₂OR³, F, Cl, —CN, NO₂, NR³R^(3a), CH₂NR³R^(3a), C(O)R³, CH₂C(O)R³,C(O)OR^(3c), CH₂C(O)OR^(3c), NR³C(O)R^(3a), C(O)NR³R^(3a),NR³C(O)NR³R^(3a), CH(═NOR^(3d)), C(═NR³)NR³R^(3a), NR³C(═NR³)NR³R^(3a),SO₂NR³R^(3a), NR³SO₂NR³R^(3a), NR³SO₂—C₁₋₄ alkyl, NR³SO₂CF₃,NR³SO₂-phenyl, S(O)_(p)CF₃, S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl, CF₃,phenyl substituted with 0-2 R⁶, naphthyl substituted with 0-2 R⁶, andbenzyl substituted with 0-2 R⁶;

R^(5a), at each occurrence, is selected from CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, OR³,CH₂OR³, NR³R^(3a), CH₂NR³R^(3a), C(O)R³, CH₂C(O)R³, C(O)OR^(3c),CH₂C(O)OR^(3c), NR³C(O)R^(3a), CH₂NR³C(O)R^(3a), C(O)NR³R^(3a),CH₂C(O)NR³R^(3a), CF₃, CF₂CF₃, phenyl substituted with 0-2 R⁶, naphthylsubstituted with 0-2 R⁶, and benzyl substituted with 0-2 R⁶, providedthat R^(5a) does not form a S—N or S(O)_(p)—C(O) bond; and

R⁶, at each occurrence, is selected from H, OH, OR², F, Cl, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃,CN, NO₂, NR²R^(2a), CH₂NR²R^(2a), C(O)R^(2b), CH₂C(O)R^(2b),NR²C(O)R^(2b), NR²C(O)NR²R^(2a), C(═NH)NH₂, NHC(═NH)NH₂, SO₂NR²R^(2a),NR²SO₂NR²R^(2a), and NR²SO₂C₁₋₄ alkyl.

In a tenth embodiment, the present invention provides a novel compoundor a stereoisomer or pharmaceutically acceptable salt, solvate, orprodrug form thereof, wherein the compound is selected from:

G is substituted with 1 R^(a) and is selected from the following group,wherein R^(a) is attached adjacent to the point of attachment of G:

R^(a) is R(CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₁R^(c);

R^(b) is selected from C(O)NR³, S(O)₂NR³, NR³C(O), and NR³S(O)₂;

R^(c) is selected from H, OR³, NR³C(O)R³, C(O)NR³R^(3a), C₅₋₁₀carbocycle substituted with 0-2 R⁴, and 5-10 membered heterocyclesubstituted with 0-2 R⁴ and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p);

provided that when the (CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₁ portion ofR^(a) is absent, then R^(c) is selected from NR³C(O)R³, C₅₋₁₀ carbocyclesubstituted with 0-2 R⁴, and 5-10 membered heterocycle substituted with0-2 R⁴ and consisting of: carbon atoms and 1-4 heteroatoms selected fromthe group consisting of N, O, and S(O)_(p);

further provided that the (CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₄R^(c) portionof R^(a) is other than (CR⁸R^(2b))₀₋₃-unsubstituted-phenyl or(CR⁸R⁹)₀₋₃-unsubstituted-phenyl;

G₁ is absent or is selected from (CR³R^(3a))₁₋₃, CR³═CR³,(CR³R^(3a))_(u)C(O)(CR³R^(3a))_(w), (CR³R^(3a))_(u)O(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)C(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)C(O)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)C(O)(CR³R^(3a))_(u)C(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(CR³R^(3a))_(w), (CR³R^(3a))_(u)S(O)(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(O)₂(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)S(O)₂(CR³R^(3a))_(w), and(CR³R^(3a))_(u)S(O)₂NR^(3b)(CR³R^(3a))_(w), wherein u+w total 0, 1, or2, wherein the right side of G₁ is attached to ring G, provided that G₁does not form a N—S, NCH₂N, NCH₂O, or NCH₂S bond with either group towhich it is attached;

A is selected from one of the following carbocyclic and heterocyclicgroups which are substituted with 0-2 R⁴; cyclohexyl, phenyl,piperidinyl, piperazinyl, pyridyl, pyrimidyl, furanyl, morpholinyl,thienyl, pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl, thiazolyl,isothiazolyl, pyrazolyl, imidazolyl, 1,2,3-oxadiazolyl,1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl,1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl,1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl,1,3,4-triazolyl, benzofuranyl, benzothiofuranyl, indolinyl, indolyl,benzimidazolyl, benzoxazolyl, benzthiazolyl, indazolyl, benzisoxazolyl,benzisothiazolyl, and isoindazolyl;

B¹ is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, —(CH₂)₀₋₁—C₅₋₆carbocycle substituted with 0-2 R^(4b), and —(CH₂)₀₋₁-5-6 memberedheterocycle consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p) and substituted with 0-2R^(4b);

B² is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, C(O)R^(2e),C(O)NR^(2d)R^(2d), SO₂NR^(2d)R^(2d), and S(O)_(p)R^(5a);

B³ is selected from H, C₁₋₆ alkyl substituted with 0-1 R^(4c),—(CH₂)₀₋₁-3-6 membered carbocycle substituted with 0-1 R⁵, and a—(CH₂)₀₋₁-5-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-1 R⁵;

B⁴ is selected from H, SO₂R^(3b) and OR²;

B⁵ is NR²R^(2f);

ring Q is a 5-6 membered ring consisting of, in addition to theN—CR^(4d)═N group shown, carbon atoms and 0-2 heteroatoms selected fromN, O, and S(O)_(p), and the ring is substituted with an additional 0-2R^(4d);

Q⁴ is selected from C═O and SO₂;

ring Q³ is a 5-7 membered ring consisting of, in addition to the N-Q⁴group shown, carbon atoms and 0-2 heteroatoms selected from NR^(4c), O,S, S(O), and S(O)₂, wherein: 0-2 double bonds are present within thering and the ring is substituted with 0-2 R^(4a);

alternatively, ring Q³ is a 5-7 membered ring to which another ring isfused, wherein: the 5-7 membered ring consists of, in addition to theshown amide group, carbon atoms and 0-2 heteroatoms selected fromNR^(4c), O, S, S(O), and S(O)₂, and 0-1 double bonds are present withinthe ring; the fusion ring is phenyl or a 5-6 membered heteroaromaticconsisting of carbon atoms and 1-2 heteroatoms selected from NR^(4c), O,and S;

ring Q³, which includes the 5-7 membered ring and the fusion ring, issubstituted with 0-3 R^(4a);

ring Q⁵, is a C₃₋₆ monocyclic carbocycle or 5-6 membered monocyclicheterocycle, wherein the carobocycle or heterocycle consists of carbonatoms and 0-2 heteroatoms selected from N, O, and S(O)_(p), thecarbocycle or heterocycle further comprises 0-1 double bonds and 0-1carbonyl groups, and the carbocycle or heterocycle is substituted with0-2 R⁴;

X is selected from —(CR²R^(2a))₁₋₂—, —C(═NR¹)—, —C(O)—, —S(O)₂—,—NR²S(O)₂—, —NR²S(O)₂—, —NR²C(O)—, —C(O)NR²—, —NR²C(O)CR²R^(2a)—,—NR²C(O)NR²—, NR², —NR²CR²R^(2a)—, —CR²R^(2a)NR²—, O, —OCR²R^(2a)—, and—CR²R^(2a)O—;

Y is selected from: CY¹Y²R^(4a), NR³R^(3a), and C(O)NR³R^(3a);

Y¹ and Y² are independently C₁₋₂ alkyl substituted with 0-2 R⁴;

alternatively, Y is selected from one of the following carbocyclic andheterocycles that are substituted with 1 R^(4a) and 0-1 R⁴: cyclopentyl,cyclohexyl, phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl,furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl,isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, oxadiazole,thiadiazole, triazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole,1,2,5-oxadiazole, 1,3,4-oxadiazole, 1,2,3-thiadiazole,1,2,4-thiadiazole, 1,2,5-thiadiazole, 1,3,4-thiadiazole, 1,2,3-triazole,1,2,4-triazole, 1,2,5-triazole, 1,3,4-triazole, benzofuran,benzothiofuran, indole, benzimidazole, benzimidazolone, benzoxazole,benzthiazole, indazole, benzisoxazole, benzisothiazole, and isoindazole;

R^(1a) is selected from H, R^(1b), CH(CH₃)R^(1b), C(CH₃)₂R^(1b),CH₂R^(1b), and CH₂CH₂R^(1b), provided that R^(1a) forms other than anN-halo, N—S, or N—CN bond;

alternatively, when two R^(1a) groups are attached to adjacent atoms,together with the atoms to which they are attached they form a 5-6membered ring consisting of: carbon atoms and 0-2 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), this ring beingsubstituted with 0-2 R^(4b) and 0-3 ring double bonds;

R^(1b) is selected from H, CH₃, CH₂CH₃, F, Cl, Br, —CN, —CHO, CF₃, OR²,NR²R^(2a), C(O)R^(2b), CO₂R^(2b), OC(O)R², CO₂R^(2a), S(O)_(p)R²,NR²(CH₂)_(r)OR², NR²C(O)R^(2b), C(O)NR²R^(2a), SO₂NR²R^(2a), NR²SO₂R²,phenyl substituted with 0-2 R^(4b), and 5-6 membered aromaticheterocycle consisting of carbon atoms and from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-2 R^(4b), provided that R^(1b) forms other than an O—O, N-halo, N—S,or N—CN bond;

R², at each occurrence, is selected from H, CF₃, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, phenyl substituted with 0-2 R^(4b), a benzyl substituted with0-2 R^(4b), and a 5-6 membered aromatic heterocycle consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p), and substituted with 0-2 R^(4b);

R^(2a), at each occurrence, is selected from H, CF₃, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, benzyl substituted with 0-2 R^(4b), phenylsubstituted with 0-2 R^(4b), and 5-6 membered aromatic heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p), and substituted with 0-2 R^(4b);

alternatively, NR²R^(2a) forms a 5 or 6 membered saturated, partiallysaturated or unsaturated ring substituted with 0-2 R^(4b) and consistingof: 0-1 additional heteroatoms selected from the group consisting of N,O, and S(O)_(p);

R^(2b), at each occurrence, is selected from CF₃, C₁₋₄ alkoxy, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzyl substituted with 0-2 R^(4b), phenylsubstituted with 0-2 R^(4b), and 5-6 membered aromatic heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p), and substituted with 0-2 R^(4b);

R^(2c), at each occurrence, is selected from CF₃, OH, OCH₃, OCH₂CH₃,OCH₂CH₂CH₃, OCH(CH₃)₂, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzylsubstituted with 0-2 R^(4b), phenyl substituted with 0-2 R^(4b), and 5-6membered aromatic heterocycle containing from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-2 R^(4b);

R^(2d), at each occurrence, is selected from H, R^(4c), C₁₋₄ alkylsubstituted with 0-2 R^(4c), C₃₋₆ carbocycle substituted with 0-2R^(4c), —(CR³R^(3a))—C₃₋₆ carbocycle substituted with 0-2 R^(4c), 5-6membered heterocycle substituted with 0-2 R^(4c) and consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p), and —(CR³R^(3a))-5-6 membered heterocyclesubstituted with 0-2 R^(4c) and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),provided that R^(2d) forms other than a N-halo, N—C-halo, S(O)_(p)-halo,O-halo, N—S, S—N, S(O)_(p)—S(O)_(p), S—O, O—N, O—S, or O—O moiety;

R^(2e), at each occurrence, is selected from H, R^(4c), C₁₋₄ alkylsubstituted with 0-2 R^(4c), C₃₋₆ carbocycle substituted with 0-2R^(4c), —(CR³R^(3a))—C₃₋₆ carbocycle substituted with 0-2 R^(4c), 5-6membered heterocycle substituted with 0-2 R^(4c) and consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p), and —(CR³R^(3a))-5-6 membered heterocyclesubstituted with 0-2 R^(4c) and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),provided that R^(2e) forms other than a C(O)-halo or C(O)—S(O)_(p)moiety;

R^(2f), at each occurrence, is selected from H, CF₃, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, OCH₃, and benzyl;

alternatively, NR²R^(2f) forms a 5-6 membered ring consisting of: carbonatoms and 0-2 additional heteroatoms selected from N, O, and S(O)_(p),and this ring is substituted with 0-2 R^(4b);

alternatively, B⁴ and R^(2f) combine to form a 5-6 membered ringconsisting of: carbon atoms and 0-1 additional heteroatoms selected fromN, O, and S(O)_(p), and this ring is substituted with 0-2 R^(4b) and theR² group of NR²R^(2f), in addition to the groups recited below, can beSO₂R^(3b);

R^(3b), at each occurrence, is selected from H, CF₃, CH₃, CH₂CH₃,CH₂CH₂CH₃, and CH(CH₃)₂;

R⁴, at each occurrence, is selected from H, ═O, CH₂OR², (CH₂)₂OR², OR²,F, Cl, Br, I, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, —CN, NO₂, NR²R^(2a), CH₂NR²R^(2a),(CH₂)₂NR²R^(2a), C(O)R^(2c), NR²C(O)R^(2b), C(O)NR²R^(2a),NR²C(O)NR²R^(2a), SO₂NR²R^(2a), CF₃, and CF₂CF₃;

R^(4a) is selected from —(CR³R^(3g))_(r)-5-6 membered carbocyclesubstituted with 0-3 R^(4c), —(CR³R^(3g))_(r)-5-6 membered heterocyclesubstituted with 0-3 R^(4c) and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),(CR³R^(3g))_(r)NR^(2d)R^(2d), (CR³R^(3g))_(r)N(→O)R^(2d)R^(2d),(CR³R^(3g))_(r)OR^(2d), (CR³R^(3g))_(r)—NR^(2d)C(O)R^(2e),(CR³R^(3g))_(r)—C(O)R^(2e), (CR³R^(3g))_(r)—OC(O)R^(2e),(CR³R^(3g))_(r)—C(O)NR^(2d)R^(2d), (CR³R^(3g))_(r)—C(O)OR^(2d),(CR³R^(3g))_(r)—NR^(2d)C(O)NR^(2d)R^(2d),(CR³R^(3g))_(r)—NR^(2d)C(O)OR^(2d), (CR³R^(3g))_(r)—SO₂NR^(2d)R^(2d),(CR³R^(3g))_(r)—NR^(2d)SO₂R^(2d), and (CR³R^(3g))_(r)—S(O)_(p)R^(2d),provided that S(O)_(p)R^(2d) forms other than S(O)₂H or S(O)H;

R^(4b), at each occurrence, is selected from H, ═O, OR³, CH₂OR³, F, Cl,CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, —CN, NO₂, NR³R^(3a), CH₂NR³R^(3a),C(O)R³, CH₂C(O)R³, C(O)OR^(3c), CH₂—C(O)OR^(3c), NR³C(O)R^(3a),CH₂NR³C(O)R^(3a), C(O)NR³R^(3a), CH₂—C(O)NR³R^(3a), SO₂NR³R^(3a),CH₂SO₂NR³R^(3a), NR³SO₂—C₁₋₄ alkyl, CH₂NR³SO₂—C₁₋₄ alkyl, NR³SO₂-phenyl,CH₂NR³SO₂-phenyl, S(O)_(p)CF₃, CH₂S(O)_(p)CF₃, S(O)_(p)—C₁₋₄ alkyl,CH₂S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl, CH₂S(O)_(p)-phenyl, and CF₃;

R^(4c), at each occurrence, is selected from ═O, OR², (CR³R^(3a))OR², F,(CR³R^(3a))F, Br, (CR³R^(3a))Br, Cl, (CR³R^(3a))Cl, CF₃, (CR³R^(3a))CF₃,C₂₋₃ alkenyl, C₂₋₃ alkynyl, C₁₋₄ alkyl, —CN, (CR³R^(3a))CN, NO₂,(CR³R^(3a))NO₂, NR²R^(2a), (CR³R^(3a))NR²R^(2a), N(→O)R²R^(2a),(CR³R^(3a))N(→O)R²R^(2a), C(O)R^(2c), (CR³R^(3a))C(O)R^(2c),NR²C(O)R^(2b), (CR³R^(3a))NR²C(O)R^(2b), C(O)NR²R^(2a),(CR³R^(3a))C(O)NR²R^(2a), NR²C(O)NR²R^(2a), (CR³R^(3a))NR²C(O)NR²R^(2a),SO₂NR²R^(2a), (CR³R^(3a))SO₂NR²R^(2a), NR²SO₂NR²R^(2a),(CR³R^(3a))NR²SO₂NR²R^(2a), NR²SO₂R^(5a), (CR³R^(3a))NR²SO₂R^(5a),S(O)_(p)R^(5a), (CR³R^(3a))S(O)_(p)R^(5a), CF₃, CF₂CF₃, C₃₋₁₀ carbocyclesubstituted with 0-2 R^(4b), (CR³R^(3a))C₃₋₁₀ carbocycle substitutedwith 0-2 R^(4b), 5-10 membered heterocycle consisting of carbon atomsand from 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p) and substituted with 0-2 R^(4b), and (CR³R^(3a))-5-10 memberedheterocycle consisting of carbon atoms and from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p) and substituted with 0-2R^(4b);

R^(4d), at each occurrence, is selected from H, CH₂OR², OR², CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃,C(CH₃)₃, —CN, NO₂, CH₂NR²R^(2a), NR²R^(2a), C(O)R^(2c), NR²C(O)R^(2b),C(O)NR²R^(2a), NR²C(O)NR²R^(2a), NR²SO₂R⁵, SO₂NR²R^(2a), 6 memberedcarbocycle substituted with 0-1 R⁵, and a 5-6 membered heterocycleconsisting of: carbon atoms and 1-2 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p) and substituted with 0-1 R⁵;

R⁵, at each occurrence, is selected from H, ═O, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, OR³, CH₂OR³, F, Cl, —CN, NO₂, NR³R^(3a), CH₂NR³R^(3a), C(O)R³,CH₂C(O)R³, C(O)OR^(3c), CH₂C(O)OR^(3c), NR³C(O)R^(3a), C(O)NR³R^(3a),SO₂NR³R^(3a), NR³SO₂—C₁₋₄ alkyl, NR³SO₂CF₃, NR³SO₂-phenyl, S(O)_(p)CF₃,S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl, CF₃, phenyl substituted with 0-2R⁶, naphthyl substituted with 0-2 R⁶, and benzyl substituted with 0-2R⁶; and

R⁶, at each occurrence, is selected from H, OH, OR², F, Cl, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, —CN, NO₂, NR²R^(2a), CH₂NR²R^(2a), C(O)R^(2b),CH₂C(O)R^(2b), NR²C(O)R^(2b), SO₂NR²R^(2a), and NR²SO₂C₁₋₄ alkyl.

In an eleventh embodiment, the present invention provides a novelcompound or a stereoisomer or pharmaceutically acceptable salt, solvate,or prodrug form thereof, within the scope of the tenth embodiment,wherein:

G is substituted with 1 R^(a) wherein R^(a) is attached adjacent to thepoint of attachment of G:

R^(a) is R^(b)(CR⁸R^(2b))₀₋₃R^(b) ₀₋₁R^(c);

R^(b) is C(O)NR³;

R^(c) is selected from H, OR³, C₅₋₁₀ carbocycle substituted with 0-2 R⁴,and 5-10 membered heterocycle substituted with 0-2 R⁴ and consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p);

provided that when the (CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₁ portion ofR^(a) is absent, then R^(c) is selected from C₅₋₁₀ carbocyclesubstituted with 0-2 R⁴ and 5-11 membered heterocycle substituted with0-2 R⁴ and consisting of: carbon atoms and 1-4 heteroatoms selected fromthe group consisting of N, O, and S(O)_(p);

further provided that the (CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₄R^(c) portionof R^(a) is other than (CR⁸R^(2b))₀₋₃-unsubstituted-phenyl or(CR⁸R⁹)₀₋₃-unsubstituted-phenyl;

G₁ is absent or is selected from CH₂, CH₂CH₂, CH₂O, OCH₂, NH, CH₂NH,NHCH₂, CH₂C(O), C(O)CH₂, C(O)NH, NHC(O), CH₂S(O)₂, S(O)₂(CH₂), SO₂NH,and NHSO₂, wherein the right side of G₁ is attached to ring G, providedthat G₁ does not form a N—S, NCH₂N, NCH₂O, or NCH₂S bond with eithergroup to which it is attached;

A is selected from cyclohexyl, indolinyl, piperidinyl, piperazinyl,phenyl, pyridyl, and pyrimidyl, and is substituted with 0-2 R⁴;

B is selected from Y, N(B¹)C(O)C(R³R^(3g))NB²B³,

provided that Z and B are attached to different atoms on A, the R^(4d)shown is other than OH, and that the A-X—N moiety forms other than aN—N—N group;

B¹ is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, and CH(CH₃)₂;

B² is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, and CH(CH₃)₂;

B³ is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, C₂₋₅ alkyl substituted with 1R^(4c), —(CH₂)₀₋₁-3-6 membered carbocycle substituted with 0-1 R⁵, and a—(CH₂)₀₋₁-5-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-1 R⁵;

B⁴ is selected from H, SO₂R^(3b), and OR²;

B⁵ is NR²R^(2f);

ring Q is a 5-6 membered ring consisting of, in addition to the

N—CR^(4d)═N group shown, carbon atoms and 0-1 heteroatoms selected fromN, O, and S(O)_(p), and the ring is substituted with an additional 0-2R^(4d);

Q⁴ is selected from C═O and SO₂;

ring Q³ is a 6-7 membered ring consisting of, in addition to the N-Q⁴group shown, carbon atoms and 0-1 heteroatoms selected from NR^(4c), O,S, S(O), and S(O)₂, wherein: 0-2 double bonds are present within thering and the ring is substituted with 0-2 R⁴;

alternatively, ring Q³ is a 5-7 membered ring to which another ring isfused, wherein: the 5-7 membered ring consists of, in addition to theshown amide group, carbon atoms and 0-1 heteroatoms selected fromNR^(4c), O, S, S(O), and S(O)₂, and 0-1 double bonds are present withinthe ring; the fusion ring is phenyl;

ring Q³, which includes the 5-7 membered ring and the fusion ring, issubstituted with 0-2 R⁴;

ring Q⁵ is substituted with 0-1 R⁴ and is selected from cyclopropyl,cyclobutyl, cyclopentyl, cyclopentanonyl, cyclohexyl, cyclohexanonyl,pyrrolidinyl, pyrrolidinonyl, piperidinyl, piperidinonyl,tetrahydrofuranyl, and tetrahydropyranyl;

X is selected from CH₂, C(O), —S(O)₂—, —NHC(O)—, —C(O)NH—, —CH₂NH—, O,and —CH₂O—;

Y is selected from N(CH₃)₂, C(O)(CH₃)₂, C(CH₃)₂R^(4a) andC(CH₂CH₃)₂R^(4a);

altneratively, Y is selected from phenyl, pyridyl, pyrrolidino,N-pyrrolidino-carbonyl, morpholino, N-morpholino-carbonyl,1,2,3-triazolyl, imidazolyl, and benzimidazolyl, and is substituted with1 R^(4a) and 0-1 R⁴;

R^(1a), at each occurrence, is selected from H, R^(1b), CH(CH₃)R^(1b),C(CH₃)₂R^(1b), and CH₂R^(1b), provided that R^(1a) forms other than anN-halo, N—S, or N—CN bond;

R^(1b) is selected from CH₃, CH₂CH₃, F, Cl, Br, —CN, CF₃, OR²,NR²R^(2a), C(O)R^(2b), CO₂R^(2b), CO₂R^(2a), S(O)_(p)R², C(O)NR²R^(2a),SO₂NR²R^(2a), NR²SO₂R², and 5-6 membered aromatic heterocycle consistingof carbon atoms and from 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p), and substituted with 0-2 R^(4b),provided that R^(1b) forms other than an O—O, N-halo, N—S, or N—CN bond;

R², at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, phenyl substituted with 0-1 R^(4b), benzyl substituted with0-1 R^(4b), and 5-6 membered aromatic heterocycle consisting of: carbonatoms and 1-4 heteroatoms selected from the group consisting of N, O,and S(O)_(p), and substituted with 0-1 R^(4b);

R^(2a), at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, benzyl substituted with 0-1 R^(4b), phenyl substituted with0-1 R^(4b), and 5-6 membered aromatic heterocycle consisting of: carbonatoms and 1-4 heteroatoms selected from the group consisting of N, O,and S(O)_(p), and substituted with 0-1 R^(4b);

alternatively, NR²R^(2a) forms a 5 or 6 membered saturated, partiallysaturated or unsaturated ring substituted with 0-1 R^(4b) and consistingof: 0-1 additional heteroatoms selected from the group consisting of N,O, and S(O)_(p);

R^(2b), at each occurrence, is selected from OCH₃, OCH₂CH₃, OCH₂CH₂CH₃,OCH(CH₃)₂, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzyl substituted with 0-1R^(4b), phenyl substituted with 0-1 R^(4b), and 5-6 membered aromaticheterocycle consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-1 R^(4b);

R^(2c), at each occurrence, is selected from OH, OCH₃, OCH₂CH₃,OCH₂CH₂CH₃, OCH(CH₃)₂, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzylsubstituted with 0-1 R^(4b), phenyl substituted with 0-1 R^(4b), and 5-6membered aromatic heterocycle containing from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-1 R^(4b);

R^(2d), at each occurrence, is selected from H, R^(4c), C₁₋₄ alkylsubstituted with 0-2 R^(4c), C₃₋₆ carbocycle substituted with 0-2R^(4c), —(CH₂)—C₃₋₆ carbocycle substituted with 0-2 R^(4c), 5-6 memberedheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), and —(CH₂)-5-6 membered heterocycle substituted with 0-2R^(4c) and consisting of: carbon atoms and 1-4 heteroatoms selected fromthe group consisting of N, O, and S(O)_(p), provided that R^(2d) formsother than a N-halo, N—C-halo, S(O)_(p)-halo, O-halo, N—S, S—N,S(O)_(p)—S(O)_(p), S—O, O—N, O—S, or O—O moiety;

R^(2e), at each occurrence, is selected from H, R^(4c), C₁₋₄ alkylsubstituted with 0-2 R^(4c), C₃₋₆ carbocycle substituted with 0-2R^(4c), —(CH₂)—C₃₋₆ carbocycle substituted with 0-2 R^(4c), 5-6 memberedheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), and —(CH₂)-5-6 membered heterocycle and consisting of: carbonatoms and 1-4 heteroatoms selected from the group consisting of N, O,and S(O)_(p), provided that R^(2e) forms other than a C(O)-halo orC(O)—S(O)_(p) moiety;

R^(2f) at each occurrence, is selected from H, CH₃, CH₂CH₃, OCH₃, andbenzyl;

alternatively, NR²R^(2f) forms a 5-6 membered ring consisting of: carbonatoms and 0-1 additional heteroatoms selected from N, O, and S(O)_(p),and this ring is substituted with 0-1 R^(4b);

alternatively, B⁴ and R^(2f) combine to form a 5 membered ringconsisting of: carbon atoms and 0-1 additional heteroatoms selected fromN, O, and S(O)_(p), and this ring is substituted with 0-2 R^(4b) and theR² group of NR²R^(2f), in addition to the groups recited below, can beSO₂R^(3b);

R^(3b), at each occurrence, is selected from H and CH₃;

R⁴, at each occurrence, is selected from H, ═O, OH, OR², CH₂OR²,(CH₂)₂OR², F, Br, Cl, I, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, NR²R^(2a), CH₂NR²R^(2a),(CH₂)₂NR²R^(2a), C(O)R^(2c), NR²C(O)R^(2b), C(O)NR²R^(2a), SO₂NR²R^(2a),CF₃, and CF₂CF₃;

R^(4a) is selected from —(CR³R^(3g))_(r)-5-6 membered carbocyclesubstituted with 0-3 R^(4c), —(CR³R^(3g))_(r)-5-6 membered heterocyclesubstituted with 0-3 R^(4c) and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),(CR³R^(3g))_(r)NR^(2d)R^(2d), (CR³R^(3g))_(r)N(→O)R^(2d)R^(2d),(CR³R^(3g))_(r)OR^(2d), (CR³R^(3g))_(r)—C(O)NR^(2d)R^(2d),(CR³R^(3g))_(r)—NR^(2d)C(O)R^(2e), (CR³R^(3g))_(r)—C(O)R^(2e),(CR³R^(3g))_(r)—NR^(2d)C(O)NR^(2d)R^(2d),(CR³R^(3g))_(r)—NR^(2d)C(O)OR^(2d), (CR³R^(3g))_(r)—NR^(2d)SO₂R^(2d),and (CR³R^(3g))_(r)—S(O)_(p)R^(2d), provided that S(O)_(p)R^(2d) formsother than S(O)₂H or S(O)H;

R^(4b), at each occurrence, is selected from H, ═O, OR³, CH₂OR³, F, Cl,CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, —CN, NO₂, NR³R^(3a), CH₂NR³R^(3a),C(O)R³, C(O)OR^(3c), NR³C(O)R^(3a), C(O)NR³R^(3a), SO₂NR³R^(3a),NR³SO₂—C₁₋₄ alkyl, NR³SO₂-phenyl, S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl,and CF₃;

R^(4c), at each occurrence, is selected from ═O, OR², CH₂OR², F, Br, Cl,CF₃, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂,CH(CH₃)CH₂CH₃, C(CH₃)₃, C₂₋₃ alkenyl, C₂₋₃ alkynyl, —CN, NO₂, NR²R^(2a),CH₂NR²R^(2a), N(→O)R²R^(2a), CH₂N(→O)R²R^(2a), C(O)R^(2c),CH₂C(O)R^(2c), NR²C(O)R^(2b), CH₂NR²C(O)R^(2b), C(O)NR²R^(2a),CH₂C(O)NR²R^(2a), SO₂NR²R^(2a), CH₂SO₂NR²R^(2a), NR²SO₂R^(5a),CH₂NR²SO₂R^(5a), S(O)_(p)R^(5a), CH₂S(O)_(p)R^(5a), CF₃, CF₂CF₃, C₃₋₆carbocycle substituted with 0-2 R^(4b), (CH₂)C₃₋₆ carbocycle substitutedwith 0-2 R^(4b), 5-6 membered heterocycle consisting of carbon atoms andfrom 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p) and substituted with 0-2 R^(4b), and (CH₂)-5-6 memberedheterocycle consisting of carbon atoms and from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p) and substituted with 0-2R^(4b);

R^(4d), at each occurrence, is selected from H, CH₂OR², OR², CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃,C(CH₃)₃, CH₂NR²R^(2a), NR²R^(2a), C(O)R^(2c), NR²C(O)R^(2b),C(O)NR²R^(2a), SO₂NR²R^(2a), NR²SO₂R⁵, phenyl substituted with 0-1 R⁵,and a 5-6 membered heterocycle consisting of: carbon atoms and 1heteroatom selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-1 R⁵;

R⁵, at each occurrence, is selected from H, ═O, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, OR³, CH₂OR³, F, Cl, —CN, NO₂, NR³R^(3a), CH₂NR³R^(3a), C(O)R³,C(O)OR^(3c), NR³C(O)R^(3a), C(O)NR³R^(3a), SO₂NR³R^(3a), NR³SO₂—C₁₋₄alkyl, NR³SO₂-phenyl, S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl, CF₃, phenylsubstituted with 0-2 R⁶, naphthyl substituted with 0-2 R⁶, and benzylsubstituted with 0-2 R⁶; and

R⁶, at each occurrence, is selected from H, OH, OR², F, Cl, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, —CN, NO₂, NR²R^(2a), CH₂NR²R^(2a), C(O)R^(2b),CH₂C(O)R^(2b), NR²C(O)R^(2b), and SO₂NR²R^(2a).

In a twelfth embodiment, the present invention provides a novel compoundor a stereoisomer or pharmaceutically acceptable salt, solvate, orprodrug form thereof, within the scope of the eleventh embodiment,wherein:

G₁ is absent or is selected from CH₂NH, NHCH₂, CH₂C(O), C(O)CH₂, C(O)NH,NHC(O), NHC(O)NH, CH₂S(O)₂, S(O)₂(CH₂), SO₂NH, and NHSO₂, wherein theright side of G₁ is attached to ring G, provided that G₁ does not form aN—S, NCH₂N, NCH₂O, or NCH₂S bond with either group to which it isattached;

A is selected from the group: cyclohexyl, indolinyl, phenyl, 2-pyridyl,3-pyridyl, 2-pyrimidyl, 2-Cl-phenyl, 3-Cl-phenyl, 2-F-phenyl,3-F-phenyl, 2-methylphenyl, 2-aminophenyl, and 2-methoxyphenyl;

B is selected from Y, N(B¹)C(O)C(R³R^(3g))NB²B³,

provided that Z and B are attached to different atoms on A and that theR^(4d) shown is other than OH;

B¹ is selected from H, CH₃, CH₂CH₃, and CH₂CH₂CH₃;

B² is selected from H, CH₃, and CH₂CH₃;

B³ is selected from CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,C(CH₃)₃, CH(CH₃)CH₂CH(CH₃)₂, CH₂CH₂OH, CH(CH₃)CH₂OH, CH(phenyl)CH₂CH₃,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and CH₂-cyclopropyl;

is attached to a different atom on A than M and is selected from thegroup:

ring Q⁵ is selected from cyclopropyl, cyclobutyl, cyclopentyl,2-cyclopentanonyl, cyclohexyl, 2-cyclohexanonyl, pyrrolidinyl (attachedto A and R^(4a) at the 2-position), pyrrolidinyl (attached to A andR^(4a) at the 3-position), 2-pyrrolidinonyl (attached to A and R^(4a) atthe 3-position), piperidinyl (attached to A and R^(4a) at the4-position), 4-piperdinonyl (attached to A and R^(4a) at the3-position), tetrahydrofuranyl, and tetrahydropyranyl (attached to A andR^(4a) at the 4-position);

Y is selected from N(CH₃)₂, C(O)(CH₃)₂, C(CH₃)₂R^(4a) andC(CH₂CH₃)₂R^(4a);

alternatively, Y is selected from phenyl, pyridyl, 1,2,3-triazolyl,imidazolyl, and benzimidazolyl, and is substituted with 1 R^(4a);

R^(1a), at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH₂F, CH₂Cl, Br, CH₂Br, —CN, CH₂CN, CF₃, CH₂CF₃, OCH₃, CH₂OH, C(CH₃)₂OH,CH₂OCH₃, NH₂, CH₂NH₂, NHCH₃, CH₂NHCH₃, N(CH₃)₂, CH₂N(CH₃)₂, CO₂H, COCH₃,CO₂CH₃, CH₂CO₂CH₃, SCH₃, CH₂SCH₃, S(O)CH₃, CH₂S(O)CH₃, S(O)₂CH₃,CH₂S(O)₂CH₃, C(O)NH₂, CH₂C(O)NH₂, SO₂NH₂, CH₂SO₂NH₂, NHSO₂CH₃,CH₂NHSO₂CH₃, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl,pyridin-2-yl-N-oxide, pyridin-3-yl-N-oxide, pyridin-4-yl-N-oxide,imidazol-1-yl, CH₂-imidazol-1-yl, 4-methyl-oxazol-2-yl,4-N,N-dimethylaminomethyl-oxazol-2-yl, 1,2,3,4-tetrazol-1-yl,1,2,3,4-tetrazol-5-yl, CH₂-1,2,3,4-tetrazol-1-yl, andCH₂-1,2,3,4-tetrazol-5-yl, provided that R^(1a) forms other than anN-halo, N—S, or N—CN bond;

R², at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, phenyl substituted with 0-1 R^(4b), benzyl substituted with0-1 R^(4b), and 5 membered aromatic heterocycle consisting of: carbonatoms and 1-4 heteroatoms selected from the group consisting of N, O,and S(O)_(p), and substituted with 0-1 R^(4b);

R^(2a), at each occurrence, is selected from H, CH₃, and CH₂CH₃;

alternatively, NR²R^(2a) forms a 5 or 6 membered saturated, partiallysaturated or unsaturated ring substituted with 0-1 R^(4b) and consistingof: 0-1 additional heteroatoms selected from the group consisting of N,O, and S(O)_(p);

R^(2b), at each occurrence, is selected from OCH₃, OCH₂CH₃, CH₃, andCH₂CH₃;

R^(2c), at each occurrence, is selected from OH, OCH₃, OCH₂CH₃, CH₃, andCH₂CH₃;

R^(2d), at each occurrence, is selected from H, R^(4c), C₁₋₄ alkylsubstituted with 0-2 R^(4c), C₃₋₆ cycloalkyl substituted with 0-2R^(4c), phenyl substituted with 0-2 R^(4c), and 5-6 membered aromaticheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), provided that R^(2d) forms other than a N-halo, N—C-halo,S(O)_(p)-halo, O-halo, N—S, S—N, S(O)_(p)—S(O)_(p), S—O, O—N, O—S, orO—O moiety;

R^(2e), at each occurrence, is selected from H, R^(4c), C₁₋₄ alkylsubstituted with 0-2 R^(4c), C₃₋₆ cycloalkyl substituted with 0-2R^(4c), phenyl substituted with 0-2 R^(4c), and 5-6 membered aromaticheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), provided that R^(2e) forms other than a C(O)-halo orC(O)—S(O)_(p) moiety;

R^(2f), at each occurrence, is selected from H, CH₃, CH₂CH₃, and OCH₃;

alternatively, NR²R^(2f) forms a ring selected from morpholine,piperazine, piperidine, and pyrrolidine;

R⁴, at each occurrence, is selected from H, ═O, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, and C(CH₃)₃;

R^(4a) is selected from —(CH₂)_(r)-5-6 membered carbocycle substitutedwith 0-3 R^(4c), —(CH₂)_(r)-5-6 membered heterocycle substituted with0-3 R^(4c) and consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), (CH₂)_(r)NR^(2d)R^(2d),(CH₂)_(r)N(→O)R^(2d)R^(2d), (CH₂)_(r)OR^(2d),(CH₂)_(r)—C(O)NR^(2d)R^(2d), (CH₂)_(r)—NR^(2d)C(O)R^(2e),(CH₂)_(r)—C(O)R^(2e), (CH₂)_(r)—NR^(2d)C(O)NR^(2d)R^(2d),(CH₂)_(r)—NR^(2d)C(O)OR^(2d), (CH₂)_(r)—NR^(2d)SO₂R^(2d), and(CH₂)_(r)—S(O)_(p)R^(2d), provided that S(O)_(p)R^(2d) forms other thanS(O)₂H or S(O)H;

R^(4b), at each occurrence, is selected from H, ═O, OR³, CH₂OR³, F, Cl,CH₃, CH₂CH₃, NR³R^(3a), CH₂NR³R^(3a), C(O)R³, C(O)OR^(3c),NR³C(O)R^(3a), C(O)NR³R^(3a), SO₂NR³R^(3a), NR³SO₂-phenyl, S(O)₂CH₃,S(O)₂-phenyl, and CF₃;

R^(4c), at each occurrence, is selected from ═O, OH, OCH₃, OCH₂CH₃,OCH₂CH₂CH₃, OCH(CH₃)₂, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, C₂₋₃ alkenyl,C₂₋₃ alkynyl, CH₂OH, CH₂OCH₃, CH₂OCH₂CH₃, CH₂OCH₂CH₂CH₃, CH₂OCH(CH₃)₂,F, Br, Cl, CF₃, NR²R^(2a), CH₂NR²R^(2a), N(→O)R²R^(2a),CH₂N(→O)R²R^(2a), C(O)R^(2c), CH₂C(O)R^(2c), NR²C(O)R^(2b),CH₂NR²C(O)R^(2b), C(O)NR²R^(2a), CH₂C(O)NR²R^(2a), SO₂NR²R^(2a),CH₂SO₂NR²R^(2a), NR²SO₂R^(5a), CH₂NR²SO₂R^(5a), S(O)_(p)R^(5a),CH₂S(O)_(p)R^(5a), CF₃, cyclopropyl substituted with 0-1 R^(4b),cyclobutyl substituted with 0-1 R^(4b), cyclopentyl substituted with 0-1R^(4b), phenyl substituted with 0-1 R^(4b), —CH₂-cyclopropyl substitutedwith 0-1 R^(4b), —CH₂-cyclobutyl substituted with 0-1 R^(4b),—CH₂-cyclopentyl substituted with 0-1 R^(4b), benzyl substituted with0-2 R^(4b), 5-6 membered aromatic heterocycle consisting of carbon atomsand from 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p) and substituted with 0-2 R^(4b), and (CH₂)-5-6 memberedaromatic heterocycle consisting of carbon atoms and from 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p) and substitutedwith 0-2 R^(4b);

R^(4d), at each occurrence, is selected from H, OCH₃, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, NR²R^(2a), NR²C(O)R^(2b), NR²SO₂R⁵, phenyl,2-oxo-pyrrolidinyl, and 2-oxo-piperidinyl;

R⁵, at each occurrence, is selected from H, ═O, CH₃, CH₂CH₃, OR³,CH₂OR³, F, Cl, NR³R^(3a), CH₂NR³R^(3a), C(O)R³, C(O)OR^(3c),NR³C(O)R^(3a), C(O)NR³R^(3a), SO₂NR³R^(3a), NR³SO₂—C₁₋₄ alkyl,NR³SO₂-phenyl, S(O)₂—CH₃, S(O)₂-phenyl, CF₃, phenyl substituted with 0-2R⁶, naphthyl substituted with 0-2 R⁶, and benzyl substituted with 0-2R⁶; and

R⁶, at each occurrence, is selected from H, OH, OR², F, Cl, CH₃, CH₂CH₃,NR²R^(2a), CH₂NR²R^(2a), C(O)R^(2b), CH₂C(O)R^(2b), NR²C(O)R^(2b), andSO₂NR²R^(2a).

In a thirteenth embodiment, the present invention provides a novelcompound or a stereoisomer or pharmaceutically acceptable salt, solvate,or prodrug form thereof, within the scope of the twelfth embodiment,wherein:

A is selected from the group: indolinyl, phenyl, 2-pyridyl, 2-pyrimidyl,and 2-F-phenyl, wherein B is substituted at the 4-position of A, exceptwhen A is indolinyl, then B is substituted at the 6-position of A;

B is selected from:

R^(2d), at each occurrence, is selected from H, C₁₋₄ alkyl substitutedwith 0-1 R^(4c), C₃₋₆ cycloalkyl substituted with 0-2 R^(4c), phenylsubstituted with 0-2 R^(4c), and a 5-6 membered aromatic heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p), provided that R^(2d) forms other thana N-halo, N—C-halo, S(O)_(p)-halo, O-halo, N—S, S—N, S(O)_(p)—S(O)_(p),S—O, O—N, O—S, or O—O moiety;

R^(2e), at each occurrence, is selected from H, C₁₋₄ alkyl substitutedwith 0-1 R^(4c), C₃₋₆ cycloalkyl substituted with 0-2 R^(4c), phenyl,substituted with 0-2 R^(4c), and 5-6 membered aromatic heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p), provided that R^(2e) forms other thana C(O)-halo or C(O)—S(O)_(p) moiety;

R^(4a) is selected from NR^(2d)R^(2d), CH₂NR^(2d)R^(2d),CH₂CH₂NR^(2d)R^(2d), N(→O)R^(2d)R^(2d), CH₂N(→O)R^(2d)R^(2d),CH₂OR^(2d), C(O)R^(2e), C(O)NR^(2d)R^(2d), CH₂C(O)NR^(2d)R^(2d),NR^(2d)C(O)R^(2e), CH₂NR^(2d)C(O)R^(2e), NR^(2d)C(O)NR^(2d)R^(2d),CH₂NR^(2d)C(O)NR^(2d)R^(2d), NR^(2d)C(O)OR^(2d), CH₂NR^(2d)C(O)OR^(2d),NR^(2d)SO₂R^(2d), CH₂NR^(2d)SO₂R^(2d), S(O)_(p)R^(2d),CH₂S(O)_(p)R^(2d), 5-6 membered carbocycle substituted with 0-2 R^(4c),—(CH₂)-5-6 membered carbocycle substituted with 0-2 R^(4c), 5-6 memberedheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), and —(CH₂)-5-6 membered heterocycle substituted with 0-2R^(4c) and consisting of: carbon atoms and 1-4 heteroatoms selected fromthe group consisting of N, O, and S(O)_(p) provided that S(O)_(p)R^(2d)forms other than S(O)₂H or S(O)H; and

R^(4c) is selected from ═O, OH, OCH₃, OCH₂CH₃, OCH₂CH₂CH₃, OCH(CH₃)₂,CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH═CH₂, CH≡CH, CH₂OH, CH₂OCH₃,CH₂OCH₂CH₃, CH₂OCH₂CH₂CH₃, CH₂OCH(CH₃)₂, F, Br, Cl, CF₃, NR²R^(2a),CH₂NR²R^(2a), C(O)R^(2c), CH₂C(O)R^(2c), NR²C(O)R^(2b),CH₂NR²C(O)R^(2b), C(O)NR²R^(2a), CH₂C(O)NR²R^(2a), SO₂NR²R^(2a),CH₂SO₂NR²R^(2a), NR²SO₂R^(5a), CH₂NR²SO₂R^(5a), S(O)_(p)R^(5a), andCH₂S(O)_(p)R^(5a).

In a fourteenth embodiment, the present invention provides a novelcompound or a stereoisomer or pharmaceutically acceptable salt, solvate,or prodrug form thereof, within the scope of the thirteenth embodiment,wherein the compound is selected from:

P₄ is -G;

A-B is selected from:

R^(2d), at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH(CH₃)₂, CH₂CH₂CH(CH₃)₂, CH₂CCH, CH₂CH₂OH, CH₂C(O)NH₂,cyclopropyl, CH₂-cyclopropyl, cyclobutyl, cyclopentyl, and thiazolyl;

R^(2e), at each occurrence, is selected from CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH(CH₃)₂, CH₂CH₂CH(CH₃)₂, CH₂-cyclopropyl, cyclopropyl, andcyclopentyl;

R^(4a) is substituted with 0-2 R^(4c) and selected from morpholine,1,1-dioxo-thiomorpholine, dihydropyridine, piperidine, piperazine,pyrrolidine, imidazole, imidazoline, imidazolidine, oxazoline, andthiazoline; and

R^(4c) is selected from ═O, OH, OCH₃, and CH₃.

In a fifteenth embodiment, the present invention provides a novelcompound, wherein the compound is selected from the group: Examples62-102 and 105-106 or a stereoisomer or pharmaceutically acceptablesalt, solvate, or prodrug form thereof.

In another embodiment, the present invention provides a novelpharmaceutical composition, comprising: a pharmaceutically acceptablecarrier and a therapeutically effective amount of a compound of thepresent invention or a pharmaceutically acceptable salt, solvate, orprodrug form thereof.

In another embodiment, the present invention provides a novel method fortreating a thromboembolic disorder, comprising: administering to apatient in need thereof a therapeutically effective amount of a compoundof the present invention or a pharmaceutically acceptable salt, solvate,or prodrug form thereof.

In another preferred embodiment, the present invention provides a novelmethod, wherein the thromboembolic disorder is selected from the groupconsisting of arterial cardiovascular thromboembolic disorders, venouscardiovascular thromboembolic disorders, and thromboembolic disorders inthe chambers of the heart.

In another preferred embodiment, the present invention provides a novelmethod, wherein the thromboembolic disorder is selected from unstableangina, an acute coronary syndrome, atrial fibrillation, firstmyocardial infarction, recurrent myocardial infarction, ischemic suddendeath, transient ischemic attack, stroke, atherosclerosis, peripheralocclusive arterial disease, venous thrombosis, deep vein thrombosis,thrombophlebitis, arterial embolism, coronary arterial thrombosis,cerebral arterial thrombosis, cerebral embolism, kidney embolism,pulmonary embolism, and thrombosis resulting from (a) prosthetic valvesor other implants, (b) indwelling catheters, (c) stents, (d)cardiopulmonary bypass, (e) hemodialysis, or (f) other procedures inwhich blood is exposed to an artificial surface that promotesthrombosis.

In another embodiment, the present invention provides a novel method oftreating a patient in need of thromboembolic disorder treatment,comprising: administering a compound of the present invention or apharmaceutically acceptable salt form thereof in an amount effective totreat a thromboembolic disorder

In another embodiment, the present invention provides a novel method,comprising: administering a compound of the present invention or apharmaceutically acceptable salt form thereof in an amount effective totreat a thromboembolic disorder.

In another embodiment, the present invention provides a novel method fortreating a thromboembolic disorder, comprising: administering to apatient in need thereof a therapeutically effective amount of a firstand second therapeutic agent, wherein the first therapeutic agent iscompound of the present invention or a pharmaceutically acceptable saltthereof and the second therapeutic agent is at least one agent selectedfrom a second factor Xa inhibitor, an anti-coagulant agent, ananti-platelet agent, a thrombin inhibiting agent, a thrombolytic agent,and a fibrinolytic agent.

In another preferred embodiment, the present invention provides a novelmethod, wherein the second therapeutic agent is at least one agentselected from warfarin, unfractionated heparin, low molecular weightheparin, synthetic pentasaccharide, hirudin, argatrobanas, aspirin,ibuprofen, naproxen, sulindac, indomethacin, mefenamate, droxicam,diclofenac, sulfinpyrazone, piroxicam, ticlopidine, clopidogrel,tirofiban, eptifibatide, abciximab, melagatran, disulfatohirudin, tissueplasminogen activator, modified tissue plasminogen activator,anistreplase, urokinase, and streptokinase.

In another preferred embodiment, the present invention provides a novelmethod, wherein the second therapeutic agent is at least oneanti-platelet agent.

In another preferred embodiment, the present invention provides a novelmethod, wherein the anti-platelet agent is aspirin and clopidogrel.

In another preferred embodiment, the present invention provides a novelmethod, wherein the anti-platelet agent is clopidogrel.

In another embodiment, the present invention provides a novel article ofmanufacture, comprising:

-   -   (a) a first container;    -   (b) a pharmaceutical composition located within the first        container, wherein the composition, comprises: a first        therapeutic agent, comprising: a compound of the present        invention or a pharmaceutically acceptable salt form thereof;        and,    -   (c) a package insert stating that the pharmaceutical composition        can be used for the treatment of a thromboembolic disorder.

In another preferred embodiment, the present invention provides a novelarticle of manufacture, further comprising:

-   -   (d) a second container;

wherein components (a) and (b) are located within the second containerand component (c) is located within or outside of the second container.

In another embodiment, the present invention provides a novel article ofmanufacture, comprising:

-   -   (a) a first container;    -   (b) a pharmaceutical composition located within the first        container, wherein the composition, comprises: a first        therapeutic agent, comprising: a compound of the present        invention or a pharmaceutically acceptable salt form thereof;        and,    -   (c) a package insert stating that the pharmaceutical composition        can be used in combination with a second therapeutic agent to        treat a thromboembolic disorder.

In another preferred embodiment, the present invention provides a novelarticle of manufacture, further comprising:

-   -   (d) a second container;

wherein components (a) and (b) are located within the second containerand component (c) is located within or outside of the second container.

In another embodiment, the present invention provides novel compounds asdescribed above for use in therapy.

In another embodiment, the present invention provides the use of novelcompounds as described above for the manufacture of a medicament for thetreatment of a thromboembolic disorder.

The present invention may be embodied in other specific forms withoutdeparting from the spirit or essential attributes thereof. Thisinvention encompasses all combinations of preferred aspects of theinvention noted herein. It is understood that any and all embodiments ofthe present invention may be taken in conjunction with any otherembodiment or embodiments to describe additional more preferredembodiments. It is also to be understood that each individual element ofthe preferred embodiments is intended to be taken individually as itsown independent preferred embodiment. Furthermore, any element of anembodiment is meant to be combined with any and all other elements fromany embodiment to describe an additional embodiment.

Definitions

The compounds herein described may have asymmetric centers. Compounds ofthe present invention containing an asymmetrically substituted atom maybe isolated in optically active or racemic forms. It is well known inthe art how to prepare optically active forms, such as by resolution ofracemic forms or by synthesis from optically active starting materials.Many geometric isomers of olefins, C═N double bonds, and the like canalso be present in the compounds described herein, and all such stableisomers are contemplated in the present invention. Cis and transgeometric isomers of the compounds of the present invention aredescribed and may be isolated as a mixture of isomers or as separatedisomeric forms. All chiral, diastereomeric, racemic forms and allgeometric isomeric forms of a structure are intended, unless thespecific stereochemistry or isomeric form is specifically indicated. Allprocesses used to prepare compounds of the present invention andintermediates made therein are considered to be part of the presentinvention. All tautomers of shown or described compounds are alsoconsidered to be part of the present invention.

Preferably, the molecular weight of compounds of the present inventionis less than about 500, 550, 600, 650, 700, 750, or 800 grams per mole.Preferably, the molecular weight is less than about 800 grams per mole.More preferably, the molecular weight is less than about 750 grams permole. Even more preferably, the molecular weight is less than about 700grams per mole.

The term “substituted,” as used herein, means that any one or morehydrogens on the designated atom is replaced with a selection from theindicated group, provided that the designated atom's normal valency isnot exceeded, and that the substitution results in a stable compound.When a substituent is keto (i.e., ═O), then 2 hydrogens on the atom arereplaced. Keto substituents are not present on aromatic moieties. Ringdouble bonds, as used herein, are double bonds that are formed betweentwo adjacent ring atoms (e.g., C═C, C═N, or N═N). The present invention,in general, does not cover groups such as N-halo, S(O)H, and SO₂H.

The present invention is intended to include all isotopes of atomsoccurring in the present compounds. Isotopes include those atoms havingthe same atomic number but different mass numbers. By way of generalexample and without limitation, isotopes of hydrogen include tritium anddeuterium. Isotopes of carbon include C-13 and C-14.

When any variable (e.g., R⁶) occurs more than one time in anyconstituent or formula for a compound, its definition at each occurrenceis independent of its definition at every other occurrence. Thus, forexample, if a group is shown to be substituted with 0-2 R⁶, then saidgroup may optionally be substituted with up to two R⁶ groups and R⁶ ateach occurrence is selected independently from the definition of R⁶.Also, combinations of substituents and/or variables are permissible onlyif such combinations result in stable compounds.

When a bond to a substituent is shown to cross a bond connecting twoatoms in a ring, then such substituent may be bonded to any atom on thering. When a substituent is listed without indicating the atom via whichsuch substituent is bonded to the rest of the compound of a givenformula, then such substituent may be bonded via any atom in suchsubstituent. Combinations of substituents and/or variables arepermissible only if such combinations result in stable compounds.

In cases wherein there are nitrogen atoms (e.g., amines) on compounds ofthe present invention, these can be converted to N-oxides by treatmentwith an oxidizing agent (e.g., MCPBA and/or hydrogen peroxides) toafford other compounds of this invention. Thus, all shown and claimednitrogen atoms are considered to cover both the shown nitrogen and itsN-oxide (N→O) derivative.

As used herein, “alkyl” is intended to include both branched andstraight-chain saturated aliphatic hydrocarbon groups having thespecified number of carbon atoms. C₁₋₆ alkyl, is intended to include C₁,C₂, C₃, C₄, C₅, and C₆ alkyl groups. Examples of alkyl include, but arenot limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl,t-butyl, n-pentyl, and s-pentyl. “Haloalkyl” is intended to include bothbranched and straight-chain saturated aliphatic hydrocarbon groupshaving the specified number of carbon atoms, substituted with 1 or morehalogen (for example —C_(v)F_(w) where v=1 to 3 and w=1 to (2v+1)).Examples of haloalkyl include, but are not limited to, trifluoromethyl,trichloromethyl, pentafluoroethyl, and pentachloroethyl. “Alkoxy”represents an alkyl group as defined above with the indicated number ofcarbon atoms attached through an oxygen bridge. C₁₋₆ alkoxy, is intendedto include C₁, C₂, C₃, C₄, C₅, and C₆ alkoxy groups. Examples of alkoxyinclude, but are not limited to, methoxy, ethoxy, n-propoxy, i-propoxy,n-butoxy, s-butoxy, t-butoxy, n-pentoxy, and s-pentoxy. “Cycloalkyl” isintended to include saturated ring groups, such as cyclopropyl,cyclobutyl, or cyclopentyl. C₃₋₇ cycloalkyl is intended to include C₃,C₄, C₅, C₆, and C₇ cycloalkyl groups. Alkenyl” is intended to includehydrocarbon chains of either straight or branched configuration and oneor more unsaturated carbon-carbon bonds that may occur in any stablepoint along the chain, such as ethenyl and propenyl. C₂₋₆ alkenyl isintended to include C₂, C₃, C₄, C₅, and C₆ alkenyl groups. “Alkynyl” isintended to include hydrocarbon chains of either straight or branchedconfiguration and one or more triple carbon-carbon bonds that may occurin any stable point along the chain, such as ethynyl and propynyl. C₂₋₆Alkynyl is intended to include C₂, C₃, C₄, C₅, and C₆ alkynyl groups.

“Halo” or “halogen” as used herein refers to fluoro, chloro, bromo, andiodo; and “counterion” is used to represent a small, negatively chargedspecies such as chloride, bromide, hydroxide, acetate, and sulfate.

As used herein, “carbocycle” is intended to mean any stable 3, 4, 5, 6,or 7-membered monocyclic or bicyclic or 7, 8, 9, 10, 11, 12, or13-membered bicyclic or tricyclic ring, any of which may be saturated,partially unsaturated, or unsaturated (aromatic). Examples of suchcarbocycles include, but are not limited to, cyclopropyl, cyclobutyl,cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cycloheptenyl,cycloheptyl, cycloheptenyl, adamantyl, cyclooctyl, cyclooctenyl,cyclooctadienyl, [3.3.0]bicyclooctane, [4.3.0]bicyclononane,[4.4.0]bicyclodecane, [2.2.2]bicyclooctane, fluorenyl, phenyl, naphthyl,indanyl, adamantyl, and tetrahydronaphthyl. As shown above, bridgedrings are also included in the definition of carbocycle (e.g.,[2.2.2]bicyclooctane). When the term “carbocycle” is used, it isintended to include “aryl”. A bridged ring occurs when one or morecarbon atoms link two non-adjacent carbon atoms. Preferred bridges areone or two carbon atoms. It is noted that a bridge always converts amonocyclic ring into a trycyclic ring. When a ring is bridged, thesubstituents recited for the ring may also be present on the bridge.

As used herein, the term “heterocycle” or “heterocyclic group” isintended to mean a stable 5, 6, or 7-membered monocyclic or bicyclic or7, 8, 9, or 10-membered bicyclic heterocyclic ring which is saturated,partially unsaturated or unsaturated (aromatic), and which consists of:carbon atoms and 1, 2, 3, or 4 ring heteroatoms independently selectedfrom the group consisting of N, O and S and including any bicyclic groupin which any of the above-defined heterocyclic rings is fused to abenzene ring. The nitrogen and sulfur heteroatoms may optionally beoxidized (i.e., N→O and S(O)_(p)). The nitrogen atom may be substitutedor unsubstituted (i.e., N or NR wherein R is H or another substituent,if defined). The heterocyclic ring may be attached to its pendant groupat any heteroatom or carbon atom that results in a stable structure. Theheterocyclic rings described herein may be substituted on carbon or on anitrogen atom if the resulting compound is stable. A nitrogen in theheterocycle may optionally be quaternized. It is preferred that when thetotal number of S and O atoms in the heterocycle exceeds 1, then theseheteroatoms are not adjacent to one another. It is preferred that thetotal number of S and O atoms in the heterocycle is not more than 1. Asused herein, the term “aromatic heterocyclic group” or “heteroaryl” isintended to mean a stable 5, 6, or 7-membered monocyclic or bicyclic or7, 8, 9, or 10-membered bicyclic heterocyclic aromatic ring whichconsists of: carbon atoms and 1, 2, 3, or 4 heteroatoms independentlyselected from the group consisting of N, O and S. The nitrogen atom maybe substituted or unsubstituted (i.e., N or NR wherein R is H or anothersubstituent, if defined). The nitrogen and sulfur heteroatoms mayoptionally be oxidized (i.e., N→O and S(O)_(p)). It is to be noted thattotal number of S and O atoms in the aromatic heterocycle is not morethan 1. Bridged rings are also included in the definition ofheterocycle. A bridged ring occurs when one or more atoms (i.e., C, O,N, or S) link two non-adjacent carbon or nitrogen atoms. Preferredbridges include, but are not limited to, one carbon atom, two carbonatoms, one nitrogen atom, two nitrogen atoms, and a carbon-nitrogengroup. It is noted that a bridge always converts a monocyclic ring intoa trycyclic ring. When a ring is bridged, the substituents recited forthe ring may also be present on the bridge. When the term “heterocycle”is used, it is intended to include heteroaryl.

Examples of heterocycles include, but are not limited to, acridinyl,azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl,benzothiophenyl, benzoxazolyl, benzoxazolinyl, benzthiazolyl,benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl,benzimidazolinyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl,chromenyl, cinnolinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl,dihydrofuro[2,3-b]tetrahydrofuranyl, furanyl, furazanyl, imidazolidinyl,imidazolinyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl,indolizinyl, indolyl, 3H-indolyl, isatinoyl, isobenzofuranyl,isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl,isothiazolyl, isoxazolyl, methylenedioxyphenyl, morpholinyl,naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl,1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl,oxazolyl, oxindolyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl,phenazinyl, phenothiazinyl, phenoxathinyl, phenoxazinyl, phthalazinyl,piperazinyl, piperidinyl, piperidonyl, 4-piperidonyl, piperonyl,pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl,pyrazolyl, pyridazinyl, pyridooxazolyl, pyridoimidazolyl,pyridothiazolyl, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl,pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl,4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl,tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrazolyl,6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl,1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl,thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl,triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl,1,3,4-triazolyl, and xanthenyl. Also included are fused ring and spirocompounds containing, for example, the above heterocycles.

The phrase “pharmaceutically acceptable” is employed herein to refer tothose compounds, materials, compositions, and/or dosage forms which are,within the scope of sound medical judgment, suitable for use in contactwith the tissues of human beings and animals without excessive toxicity,irritation, allergic response, or other problem or complication,commensurate with a reasonable benefit/risk ratio.

As used herein, “pharmaceutically acceptable salts” refer to derivativesof the disclosed compounds wherein the parent compound is modified bymaking acid or base salts thereof. Examples of pharmaceuticallyacceptable salts include, but are not limited to, mineral or organicacid salts of basic residues such as amines; alkali or organic salts ofacidic residues such as carboxylic acids; and the like. Thepharmaceutically acceptable salts include the conventional non-toxicsalts or the quaternary ammonium salts of the parent compound formed,for example, from non-toxic inorganic or organic acids. For example,such conventional non-toxic salts include, but are not limited to, thosederived from inorganic and organic acids selected from1,2-ethanedisulfonic, 2-acetoxybenzoic, 2-hydroxyethanesulfonic, acetic,ascorbic, benzenesulfonic, benzoic, bicarbonic, carbonic, citric,edetic, ethane disulfonic, ethane sulfonic, fumaric, glucoheptonic,gluconic, glutamic, glycolic, glycollyarsanilic, hexylresorcinic,hydrabamic, hydrobromic, hydrochloric, hydroiodide, hydroxymaleic,hydroxynaphthoic, isethionic, lactic, lactobionic, lauryl sulfonic,maleic, malic, mandelic, methanesulfonic, napsylic, nitric, oxalic,pamoic, pantothenic, phenylacetic, phosphoric, polygalacturonic,propionic, salicyclic, stearic, subacetic, succinic, sulfamic,sulfanilic, sulfuric, tannic, tartaric, and toluenesulfonic.

The pharmaceutically acceptable salts of the present invention can besynthesized from the parent compound that contains a basic or acidicmoiety by conventional chemical methods. Generally, such salts can beprepared by reacting the free acid or base forms of these compounds witha stoichiometric amount of the appropriate base or acid in water or inan organic solvent, or in a mixture of the two; generally, non-aqueousmedia like ether, ethyl acetate, ethanol, isopropanol, or acetonitrileare preferred. Lists of suitable salts are found in Remington'sPharmaceutical Sciences, 18th ed., Mack Publishing Company, Easton, Pa.,1990, p 1445, the disclosure of which is hereby incorporated byreference.

In addition, compounds of formula I may have prodrug forms. Any compoundthat will be converted in vivo to provide the bioactive agent (i.e., acompound of formula I) is a prodrug within the scope and spirit of theinvention. Various forms of prodrugs are well known in the art. Forexamples of such prodrug derivatives, see:

-   -   a) Design of Prodrugs, edited by H. Bundgaard, (Elsevier, 1985),        and Methods in Enzymology, Vol. 42, at pp. 309-396, edited by K.        Widder, et. al. (Academic Press, 1985);    -   b) A Textbook of Drug Design and Development, edited by        Krosgaard-Larsen and H. Bundgaard, Chapter 5, “Design and        Application of Prodrugs,” by H. Bundgaard, at pp. 113-191        (1991);    -   c) H. Bundgaard, Advanced Drug Delivery Reviews, Vol. 8, p. 1-38        (1992);    -   d) H. Bundgaard, et al., Journal of Pharmaceutical Sciences,        Vol. 77, p. 285 (1988); and    -   e) N. Kakeya, et. al., Chem Phar Bull., Vol. 32, p. 692 (1984).

Preparation of prodrugs is well known in the art and described in, forexample, Medicinal Chemistry: Principles and Practice, ed. F. D. King,The Royal Society of Chemistry, Cambridge, UK, 1994, which isincorporated herein by reference in its entirety.

Radiolabelled compounds of the present invention, i.e., wherein one ormore of the atoms described are replaced by a radioactive isotope ofthat atom (e.g., C replaced by ¹³C or by ¹⁴C; and isotopes of hydrogeninclude tritium and deuterium), are also provided herein. Such compoundshave a variety of potential uses, e.g., as standards and reagents indetermining the ability of a potential pharmaceutical to bind to targetproteins or receptors, or for imaging compounds of this invention boundto biological receptors in vivo or in vitro.

“Stable compound” and “stable structure” are meant to indicate acompound that is sufficiently robust to survive isolation to a usefuldegree of purity from a reaction mixture, and formulation into anefficacious therapeutic agent. It is preferred that there presentlyrecited compounds do not contain a N-halo, S(O)₂H, or S(O)H group.

“Substituted” is intended to indicate that one or more hydrogens on theatom indicated in the expression using “substituted” is replaced with aselection from the indicated group(s), provided that the indicatedatom's normal valency is not exceeded, and that the substitution resultsin a stable compound. When a substituent is keto (i.e., ═O) group, then2 hydrogens on the atom are replaced.

As used herein, “treating” or “treatment” cover the treatment of adisease-state in a mammal, particularly in a human, and include: (a)preventing the disease-state from occurring in a mammal, in particular,when such mammal is predisposed to the disease-state but has not yetbeen diagnosed as having it; (b) inhibiting the disease-state, i.e.,arresting it development; and/or (c) relieving the disease-state, i.e.,causing regression of the disease state.

“Therapeutically effective amount” is intended to include an amount of acompound of the present invention that is effective when administeredalone or in combination to inhibit factor Xa. “Therapeutically effectiveamount” is also intended to include an amount of the combination ofcompounds claimed that is effective to inhibit factor Xa. Thecombination of compounds is preferably a synergistic combination.Synergy, as described, for example, by Chou and Talalay, Adv. EnzymeRegul. 1984, 22:27-55, occurs when the effect (in this case, inhibitionof factor Xa) of the compounds when administered in combination isgreater than the additive effect of the compounds when administeredalone as a single agent. In general, a synergistic effect is mostclearly demonstrated at sub-optimal concentrations of the compounds.Synergy can be in terms of lower cytotoxicity, increased antithromboticeffect, or some other beneficial effect of the combination compared withthe individual components.

The present invention further includes compositions comprising one ormore compounds of the present invention and a pharmaceuticallyacceptable carrier.

A “pharmaceutically acceptable carrier” refers to media generallyaccepted in the art for the delivery of biologically active agents toanimals, in particular, mammals. Pharmaceutically acceptable carriersare formulated according to a number of factors well within the purviewof those of ordinary skill in the art. These include, withoutlimitation: the type and nature of the active agent being formulated;the subject to which the agent-containing composition is to beadministered; the intended route of administration of the composition;and the therapeutic indication being targeted. Pharmaceuticallyacceptable carriers include both aqueous and non-aqueous liquid media,as well as a variety of solid and semi-solid dosage forms. Such carrierscan include a number of different ingredients and additives in additionto the active agent, such additional ingredients being included in theformulation for a variety of reasons, e.g., stabilization of the activeagent, binders, etc., well known to those of ordinary skill in the art.Descriptions of suitable pharmaceutically acceptable carriers, andfactors involved in their selection, are found in a variety of readilyavailable sources such as, for example, Remington's PharmaceuticalSciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, which isincorporated herein by reference in its entirety.

Synthesis

All references cited herein are hereby incorporated in their entirety byreference.

The compounds of the present invention can be prepared in a number ofways known to one skilled in the art of organic synthesis. The compoundsof the present invention can be synthesized using the methods describedbelow, together with synthetic methods known in the art of syntheticorganic chemistry, or by variations thereon as appreciated by thoseskilled in the art. Preferred methods include, but are not limited to,those described below. The reactions are performed in a solventappropriate to the reagents and materials employed and suitable for thetransformations being effected. Those skilled in the art of organicsynthesis understand that the functionality present on the moleculeshould be consistent with the transformations proposed. This willsometimes require a judgment to modify the order of the synthetic stepsor to select one particular process scheme over another in order toobtain a desired compound of the invention.

Another major consideration in the planning of any synthetic route inthis field is the judicious choice of the protecting group used forprotection of reactive functional groups present in the compoundsdescribed in this invention. An authoritative account describing themany alternatives to the trained practitioner is Greene and Wuts(Protective Groups In Organic Synthesis, Wiley and Sons, 1999).

The synthesis of compounds of the present invention that involves theusage of intermediate A-B is accomplished via standard methods known tothose skilled in the art.

Construction of compounds with general structure G-G₁-P-M-Z-A-B can beperformed in two directions: 1) From G to G-G₁-P-M (or a derivative ofP-M) then to G-G₁-P-M-Z-A-B or 2) From A-B to P-M-Z-A-B (or a derivativeof P-M) then to G-G₁-P-M-Z-A-B. The general route that involves thistype of methodology is outlined in Scheme 1. During the synthesis ofthese compounds, protecting groups to prevent cross-reaction during thecoupling conditions optionally protect the functional groups of thesubstituents. Examples of suitable blocking groups and their uses aredescribed in “The Peptides: Analysis, Synthesis, Biology”, AcademicPress, Vol. 3 (Groii, et. al. Eds., 1981). Functional grouptransformations and coupling reactions that can be used to preparecompounds of the present invention are described in “Advanced OrganicChemistry: Reaction, Mechanism, and Structure” (March, et. al. fourthEd.) and “Comprehensive Organic Transformations” (Larock, second Ed.).

Compounds of the present invention where B is Y—R^(4a) (provided that Aand R^(4a) are attached to the same carbon atom in Y and Y is C₃-C₇cycloalkyl) can be prepared as shown in Scheme 2. Commercially available4-nitrophenylacetonitrile (or properly protected4-aminophenylacetonitrile) can be used as the starting material.Alkylation with NaH, t-BuOK, NaNH₂, n-BuLi, s-BuLi, NaOEt, aq NaOH, etc.as the base, and X—(CH₂)_(n)—Y (X and Y can be Cl, Br, I, OMs, OTs, or⁺S(CH₃)₂ and n=2-6) as the alkylating reagent can afford the cycloalkylintermediate 1. Hydrolysis of the nitrile group, followed by reductionof the ester group can provide the alcohol 2. Oxidation of 2, thenreductive amination with NHR^(2d)R^(2d) can provide 3. Reduction of thenitro group or deprotection of the amino group can produce the A-Bprecursor 4, which can be coupled with 5 using standard couplingconditions as described in Scheme 1 to provide 6. When one of the R^(2d)groups is H, 6 can react with acid chlorides, carbamoyl chlorides,sulfonyl chlorides, and isocyanates to provide compounds of theinvention with structures 7, 8, 9, and 10. Alternatively, alcohol 2 canreact with alkyl halides and amines to form compounds of the inventionwith structures 11 and 12. Alcohol 2 can also be transformed into ahalide or its equivalents (X=Cl, Br, I, OMs, or OTs), followed byalkylation with a variety of alkylating reagents to afford compounds ofthe invention with structures 13, 14, and 15.

Other compounds of the present invention where Y is a cycloalkylderivative can be prepared using commercially available1-phenylcycloalkylcarboxylic acids (or 1-phenylcycloalkylcarbonitriles)as the starting materials as illustrated in Scheme 3. Nitration,followed by reduction of the NO₂ group and protection of the acid groupcan provide the A-B precursor 16, which can be coupled with 5 usingstandard coupling conditions to provide 17.

Alternatively, iodination can provide the desired para-substitutedcompound 18, which can in turn be transformed to the amine 16 viaBuchwald palladium-catalyzed amination (Tetrahedron Lett. 1997, 38,6367-6370) and to the acid 19 via paladium-catalyzed carboxylation (CO,Pd(OAc)₂, dppf). Additional A-B intermediates can be synthesized bychemical manipulation of the amino and carboxylic acid functionality in16 and 19, respectively. Compound 19 can be homologated via theArndt-Eistert methodology to afford other A-B intermediates in 20.Alternatively, the acid functionality in 19 can be reduced to thealcohol that in turn can be converted to a variety of A-B intermediates20 by procedures known to those skilled in the art. Further elaborationof these intermediates using the methods described above and by thoseknown in the art should provide compounds of the present invention.

Other compounds of the present invention where Y is a cycloalkylderivative can be prepared using organometalic reagents 21 (Zn, Mg,etc.) as starting materials as shown in Scheme 4. Reaction of 21 withproperly substituted cycloalkyl halides 22 (X=Cl, Br, I, OMs, OTs, etc.)using Pd(dba)₂/1,2-bis(diphenylphosphino)ethane (dppe) or NiCl₂(PPh₃)₂as the catalyst system can provide intermediate 23. Alternatively,Grignard reaction of 21 with cycloalkyl ketones can provide intermediate24. Further elaboration of 23 and 24 using the methods described aboveand by those known in the art should provide compounds of the presentinvention.

Compounds of the present invention where Y is a pyrrolidine orpiperidine derivative can be prepared as shown in Scheme 5.Phenylcyanoacetate can be alkylated with X—(CH₂)_(n)—Cl (X and Y=Br, I,OMs, OTs, etc. and n=2-3) to provide chloronitrile 25, which can bereduced to the corresponding primary amine, followed by cyclization inrefluxing EtOH to form 3-pyrrolidine or 3-piperdine derivatives 26.Alkylation or reductive amination can provide N-substituted intermediate27. Further elaboration using the methods described above and by thoseknown in the art should provide compounds of the present invention.

Compounds of the present invention where Y is a pyrrolidine derivativecan also be prepared as illustrated in Scheme 6. The Grignard reactionof 1-substituted 4-piperidone 28 with an appropriate arylmagnesiumhalide followed by dehydration should give tetrahydropyridine derivative29. Epoxidation followed by rearrangement with heating in borontrifluroride etherate (Chem. Pharm. Bull. 1980, 28(5), 1387-1393) canprovide pyrrolidine aldehyde 30. Alternatively, radical cyclization ofalkyl azide 31 (Tetrahedron Lett. 1997, 38, 3915-3918) can providepyrrolidine intermediate 32. Further elaboration of these intermediatesusing the methods described above and by those known in the art shouldprovide compounds of the present invention.

Compounds of the present invention where Y is a 4-piperidine derivativecan be prepared using 2-aryl acetonitriles 33 as starting materials asshown in Scheme 7. Dialkylation of 33 with bromoacetaldehyde dimethylacetal, followed by hydrolysis of the acetals and reductive aminationshould give the 4-aryl-4-cyanopiperidine 34. Further elaboration ofthese intermediates using the methods described above and by those knownin the art should provide compounds of the present invention.

Compounds of the present invention where Y is a 4-tetrahydrfuranderivative can be prepared using diol 35 as the starting material asillustrated in Scheme 8. Cyclization of 35 with HBr should give4-aryl-4-substituted tetrahydrofuran 36. Further elaboration using themethods described above and by those known in the art should providecompounds of the present invention.

Compounds of the present invention where Y is a 4-tetrahydropyranderivative can be prepared using 2-aryl acetonitriles 33 as startingmaterials as shown in Scheme 9. Alkylation of 33 with di-2-chloroethylether should give the 4-aryl-4-cyanotetrahydropyran 37. Furtherelaboration using the methods described above and by those known in theart should provide compounds of the present invention.

Compounds of the present invention where Y is a lactam derivative can beprepared using intermediate 38 as the starting material as shown inScheme 10. Reduction of the nitro or nitrile group can provide theprimary amine 39, which can be coupled intramolecularly with the acid orester to form the lactam 40. Further elaboration using the methodsdescribed above and by those known in the art should provide compoundsof the present invention.

Aminopyridyl, aminopyrimidyl, cyclohexyl, and piperidinyl A-B analogs(see structures in Scheme 11) can be prepared using routes similar tothose of Schemes 2-10 and by those known in the art. These intermediatescan then be further manipulated to compounds of the present inventionvia procedures previously described.

Compounds of the present invention (Scheme 1) where R^(4a) isCH₂CH₂NR^(2d)R^(2d) or CH₂CONR^(2d)R^(2d) can be prepared as outlined inScheme 12 and via standard methods known to those skilled in the art.The ester or nitrile intermediates 41 illustrated in Scheme 12 can besubjected to alkylation conditions, followed by other manipulations asdescribed in Schemes 2-10 to form 42. Homologation of intermediates 42with TMSCHN₂ as the reagent can afford 43. Further elaboration of 43 toform 44 and compounds of the present invention can be achieved using themethods described above and by those known in the art.

Compounds of the present invention where R^(4a) is NR^(2d)R^(2d) can beprepared as outlined in Scheme 13 and via standard methods known tothose skilled in the art. The acid intermediates 42 illustrated inScheme 13 can undergo Curtius rearrangement with DPPA in CH₂Cl₂ followedby heating in t-BuOH to afford Boc-protected cyclopropylamineintermediates 45. Alkylation of 45 with R^(2d)—I and NaH in THF followedby manipulations described previously should give amines 46. Reductiveamination of 46 with aqueous formaldehyde and NaBH₃CN in CH₃CN canafford the methyl alkyl amine analogues. On the other hand, alkylationwith dibromides using K₂CO₃ as the base can afford tertiary or cyclicamines, respectively. Further elaboration of 46 to form compounds of thepresent invention can be achieved using the methods described above andby those known in the art.

Schemes 2-13 describe how to make the A-B moieties of the presentinvention and how to couple them to prepare compounds of the presentinvention. Schemes 2-13 describe A-B wherein B is Y—R^(4a) and Y is acycloalkyl or heterocyclyl. Compounds of the present invention wherein Yis CY¹Y² can be made analogously to the cycloalkyl/heterocyclylcompounds of Schemes 2-13. For example, in Scheme 2, instead ofintermediate 1 being a cycloalkyl intermediate, it can be Y¹Y²disubstituted intermediate. This intermediate could be made by a numberof methods including di-substituting the starting4-nitrophenyl-acetonitrile by reaction with a base and a Y¹-leavinggroup and a Y²-leaving group. One of ordinary skill in the art wouldrecognize that other routes to the Y¹Y²-disubstituted intermediates areavailable. The remainder of the chemistry shown in Scheme 2 will thenfollow. In Scheme 3, instead of use the starting1-phenylcycloalkylcarboxylic acids or 1-phenylcycloalkylcarbonitriles,one could use the corresponding Y¹Y²-disubstituted intermediates. As inScheme 2, these intermediates could be prepared by di-substituting aphenylcarboxylic acid or phenylcarbonitrile. One of ordinary skill inthe art would recognize that other routes to these types of Y¹Y²disubstituted intermediate are also available. The remainder of thechemistry shown in Scheme 3 will then follow.

Compounds of the present invention wherein Y isN(B¹)C(O)C(R³R^(3g))₁₋₄NB²B³ can be made as described in Schemes 14-16.Scheme 14 describes the syntheses of an A-B intermediate via BuchwaldUllmann coupling reaction (J. Am. Chem. Soc. 2001, 123, 7727) using CuIand 1,2-cyclohexyldiamine or 1,10-phenanthroline as the catalyst.

Alternatively, the A-B intermediates containing amidesNH(B¹)C(O)C(R³R^(3g))₁₋₄NB²B³ can also be prepared from readilyavailable anilines as shown in Scheme 15.

Aminopyridyl, aminopyrimidyl, indonyl, cyclohexyl, and piperidinyl A-Banalogs (see structures in Scheme 16) can be prepared using routessimilar to those of Schemes 14-15 and by those known in the art. Theseintermediates can then be further manipulated to compounds of thepresent invention via procedures previously described.

Compounds of the present invention wherein B is a cyclic phenyl amidinoderivative can be prepared following the general procedure outlined inScheme 17. Boc-protection of the aniline followed by alkylation withchloroiodo-alkane can provide the Boc-protected intermediate. Azidedisplacement followed by reduction and deprotection can afford thediamine compound. Reaction with ethylformate, etc. can generate thecorresponding A-B intermediate. Compounds wherein R^(4a) is H, alkyl, orether can then be obtained using the methods described previously and bythose known in the art.

The diamino intermediate from Scheme 17 can also be transformed to analcohol intermediate followed by treatment with POCl₃, POBr₃, Tf₂O, oran alkylating agent. Further manipulations of these versatileintermediates to the compounds of the present invention can be achievedusing the methods described in Scheme 18 and by those known in the art.

The guanidino derivative from Scheme 18 can be converted to a number ofcompounds of the present invention by techniques known to those of skillin the art of organic synthesis, as outlined in Scheme 19.

Using the methodologies outlined above, other compounds of the presentinvention can be obtained as shown in Scheme 20 by functionalmanipulations and cyclization techniques known to those of skill in theart of organic synthesis.

Phenylamidino-sulfonyl and -carbonyl compounds of the present inventioncan be obtained from the readily available amidino compounds shown inScheme 21 below.

The chemistry leading to the compounds of the present inventiondescribed above can be implemented at various stages of the syntheticprocess. Those knowledgeable in the art may decide to prepare varioussulfonyl, carbonylamidino, or suitably protected cyclic amidinointermediates and couple these via known techniques to various templatesdescribed herein to afford compounds of the present invention.

The compounds of this invention and the intermediates described abovewherein the B group contains an oxidizable group can be oxidized, e.g.,N to N-oxide.

The functionalized G moiety of the present invention can be commerciallyavailable or can be prepared using methods known to those of ordinaryskill in the art. All of the following patents and publications areincorporated herein by reference. For compounds wherein G is a ringsubstituted with a basic moiety, one of ordinary skill in the art canlook to U.S. Pat. No. 5,939,418, U.S. Pat. No. 5,925,635, U.S. Pat. No.6,057,342, U.S. Pat. No. 6,187,797, U.S. Pat. No. 6,020,357, U.S. Pat.No. 6,060,491, U.S. Pat. No. 6,191,159, WO98/57951, WO99/32454WO00/059902, WO01/32628, WO00/39131, WO02/00651, WO02/102380,WO02/094197, USPA 2003/0078255, and USPA 2003/0018023 for startingmaterials. For compounds wherein G is a ring substituted with anon-basic group, one of ordinary skill in the art can look to U.S. Pat.No. 5,998,424, WO00/39131, WO00/059902, WO01/32628, WO02/00651,WO02/102380, WO02/094197, USPA 2003/0078255, and USPA 2003/0018023 forstarting materials. For compounds wherein G is a bicyclic moiety, one ofordinary skill in the art can look to WO98/57951 WO00/039108,WO00/39131, WO02/00651, WO02/102380, WO02/094197, USPA 2003/0078255, andUSPA 2003/0018023 for starting materials. For compounds wherein A is anindoline or similar bicycle, one of ordinary skill in the art can lookto WO01/005785 for starting materials and intermediates to which thepresent B group can be coupled or from which the present A-B groups canbe formed.

Compounds of the type where G is phenyl substituted with 0-2 R and 1-2R^(a) and M is fused pyrazolo compound may be synthesized as shown inScheme 22.

Additional compounds may be accessed where the pyrazole moiety isreplaced by other heterocycles are described in WO 00/39131 and WO03/26652.

Scheme 23 describes the synthesis of phenyl substituted pyrazoles.Additional examples may be found in WO 98/57951 and WO 99/32454.

Compounds of the type where G is phenyl substituted with 0-2 R and 1-2R^(a) and M is phenyl may be synthesized as shown in Scheme 24 forcarboxamides and Scheme 25 for sulfonamides.

One stereoisomer of a compound of Formula I may display superioractivity compared with the other. Thus, compounds of the presentinvention may be chiral and accordingly in various enantiomeric forms.They therefore may exist in racemic or in optically active form. Whenrequired, separation of the racemic material can be achieved by HPLCusing a chiral column or by a resolution using a resolving agent such asdescribed in Wilen, S. H. Tables of Resolving Agents and OpticalResolutions 1972, 308 or using enantiomerically pure acids and bases. Achiral compound of Formula I may also be directly synthesized using achiral catalyst or a chiral ligand, e.g., Jacobsen, E. Acc. Chem. Res.2000, 33, 421-431 or using other enantio- and diastereo-selectivereactions and reagents known to one skilled in the art of asymmetricsynthesis. An enantiomerically pure compound can be obtained withenantiomerically pure starting materials. Alternately, singlestereoisomers can be obtained by chiral synthesis known to the personwith skills in the art.

Utility

The compounds of this invention are inhibitors of factor Xa and areuseful as anticoagulants for the treatment or prevention ofthromboembolic disorders in mammals (i.e., factor Xa-associateddisorders). In general, a thromboembolic disorder is a circulatorydisease caused by blood clots (i.e., diseases involving fibrinformation, platelet activation, and/or platelet aggregation). The term“thromboembolic disorders” as used herein includes arterialcardiovascular thromboembolic disorders, venous cardiovascular orcerebrovascular thromboembolic disorders, and thromboembolic disordersin the chambers of the heart. The term “thromboembolic disorders” asused herein also includes specific disorders selected from, but notlimited to, unstable angina or other acute coronary syndromes, atrialfibrillation, first or recurrent myocardial infarction, ischemic suddendeath, transient ischemic attack, stroke, atherosclerosis, peripheralocclusive arterial disease, venous thrombosis, deep vein thrombosis,thrombophlebitis, arterial embolism, coronary arterial thrombosis,cerebral arterial thrombosis, cerebral embolism, kidney embolism,pulmonary embolism, and thrombosis resulting from (a) prosthetic valvesor other implants, (b) indwelling catheters, (c) stents, (d)cardiopulmonary bypass, (e) hemodialysis, or (f) other procedures inwhich blood is exposed to an artificial surface that promotesthrombosis. It is noted that thrombosis includes occlusion (e.g. after abypass) and reocclusion (e.g., during or after percutaneous transluminalcoronary angioplasty). The thromboembolic disorders may result fromconditions including but not limited to atherosclerosis, surgery orsurgical complications, prolonged immobilization, arterial fibrillation,congenital thrombophilia, cancer, diabetes, effects of medications orhormones, and complications of pregnancy. The anticoagulant effect ofcompounds of the present invention is believed to be due to inhibitionof factor Xa or thrombin.

The effectiveness of compounds of the present invention as inhibitors offactor Xa was determined using purified human factor Xa and syntheticsubstrate. The rate of factor Xa hydrolysis of chromogenic substrateS2222 (Diapharma/Chromogenix, West Chester, Ohio) was measured both inthe absence and presence of compounds of the present invention.Hydrolysis of the substrate resulted in the release of pNA, which wasmonitored spectrophotometrically by measuring the increase in absorbanceat 405 nm. A decrease in the rate of absorbance change at 405 nm in thepresence of inhibitor is indicative of enzyme inhibition. The results ofthis assay are expressed as inhibitory constant, K_(i).

Factor Xa determinations were made in 0.10 M sodium phosphate buffer, pH7.5, containing 0.20 M NaCl, and 0.5% PEG 8000. The Michaelis constant,K_(m), for substrate hydrolysis was determined at 25° C. using themethod of Lineweaver and Burk. Values of K_(i) were determined byallowing 0.2-0.5 nM human factor Xa (Enzyme Research Laboratories, SouthBend, Ind.) to react with the substrate (0.20 mM-1 mM) in the presenceof inhibitor. Reactions were allowed to go for 30 min and the velocities(rate of absorbance change vs. time) were measured in the time frame of25-30 min. The following relationship was used to calculate K_(i)values:(v _(o) −v _(s))/v _(s) =I(K _(i)(1+S/K _(m)))

-   -   where:        -   v_(o) is the velocity of the control in the absence of            inhibitor;        -   v_(s) is the velocity in the presence of inhibitor;        -   I is the concentration of inhibitor;        -   K_(i) is the dissociation constant of the enzyme:inhibitor            complex;        -   S is the concentration of substrate;        -   K_(m) is the Michaelis constant.

Compounds tested in the above assay are considered to be active if theyexhibit a K_(i) of ≦10 μM. Preferred compounds of the present inventionhave K_(i)'s of ≦1 μM. More preferred compounds of the present inventionhave K_(i)'s of ≦0.1 μM. Even more preferred compounds of the presentinvention have K_(i)'s of ≦0.01 μM. Still more preferred compounds ofthe present invention have K_(i)'s of ≦0.001 μM. Using the methodologydescribed above, a number of compounds of the present invention werefound to exhibit K_(i)'s of ≦10 μM, thereby confirming the utility ofthe compounds of the present invention as effective Xa inhibitors.

The antithrombotic effect of compounds of the present invention can bedemonstrated in a rabbit arterio-venous (AV) shunt thrombosis model. Inthis model, rabbits weighing 2-3 kg anesthetized with a mixture ofxylazine (10 mg/kg i.m.) and ketamine (50 mg/kg i.m.) are used. Asaline-filled AV shunt device is connected between the femoral arterialand the femoral venous cannulae. The AV shunt device consists of a pieceof 6-cm tygon tubing that contains a piece of silk thread. Blood willflow from the femoral artery via the AV-shunt into the femoral vein. Theexposure of flowing blood to a silk thread will induce the formation ofa significant thrombus. After 40 min, the shunt is disconnected and thesilk thread covered with thrombus is weighed. Test agents or vehiclewill be given (i.v., i.p., s.c., or orally) prior to the opening of theAV shunt. The percentage inhibition of thrombus formation is determinedfor each treatment group. The ID₅₀ values (dose which produces 50%inhibition of thrombus formation) are estimated by linear regression.

The compounds of the present invention may also be useful as inhibitorsof serine proteases, notably human thrombin, Factor VIIa, Factor IXa,Factor XIa, urokinase, plasma kallikrein, and plasmin. Because of theirinhibitory action, these compounds are indicated for use in theprevention or treatment of physiological reactions, blood coagulationand inflammation, catalyzed by the aforesaid class of enzymes.Specifically, the compounds have utility as drugs for the treatment ofdiseases arising from elevated thrombin activity such as myocardialinfarction, and as reagents used as anticoagulants in the processing ofblood to plasma for diagnostic and other commercial purposes.

Some compounds of the present invention were shown to be direct actinginhibitors of the serine protease thrombin by their ability to inhibitthe cleavage of small molecule substrates by thrombin in a purifiedsystem. In vitro inhibition constants were determined by the methoddescribed by Kettner et al. in J. Biol. Chem. 265, 18289-18297 (1990),herein incorporated by reference. In these assays, thrombin-mediatedhydrolysis of the chromogenic substrate S2238 (Helena Laboratories,Beaumont, Tex.) was monitored spectrophotometrically. Addition of aninhibitor to the assay mixture results in decreased absorbance and isindicative of thrombin inhibition. Human thrombin (Enzyme ResearchLaboratories, Inc., South Bend, Ind.) at a concentration of 0.2 nM in0.10 M sodium phosphate buffer, pH 7.5, 0.20 M NaCl, and 0.5% PEG 6000,was incubated with various substrate concentrations ranging from 0.20 to0.02 mM. After 25 to 30 min of incubation, thrombin activity was assayedby monitoring the rate of increase in absorbance at 405 nm that arisesowing to substrate hydrolysis. Inhibition constants were derived fromreciprocal plots of the reaction velocity as a function of substrateconcentration using the standard method of Lineweaver and Burk. Usingthe methodology described above, some compounds of this invention wereevaluated and found to exhibit a K_(i) of less than 10 μm, therebyconfirming the utility of the compounds of the present invention aseffective thrombin inhibitors.

The compounds are administered to a mammal in a therapeuticallyeffective amount. By “therapeutically effective amount” it is meant anamount of a compound of the present invention that, when administeredalone or in combination with an additional therapeutic agent to amammal, is effective to treat a thromboembolic condition or disease.

The compounds of the present invention can be administered alone or incombination with one or more additional therapeutic agents. By“administered in combination” or “combination therapy” it is meant thata compound of the present invention and one or more additionaltherapeutic agents are administered concurrently to the mammal beingtreated. When administered in combination each component may beadministered at the same time or sequentially in any order at differentpoints in time. Thus, each component may be administered separately butsufficiently closely in time so as to provide the desired therapeuticeffect.

Additional therapeutic agents include other anti-coagulant orcoagulation inhibitory agents, anti-platelet or platelet inhibitoryagents, thrombin inhibitors, thrombolytic or fibrinolytic agents,anti-arrythmic agents, anti-hypertensive agents, calcium channelblockers (L-type and T-type), cardiac glycosides, diruetics,mineralocorticoid receptor antagonists, phospodiesterase inhibitors,cholesterol/lipid lowering agents and lipid profile therapies,anti-diabetic agents, anti-depressants, anti-inflammatory agents(steroidal and non-steroidal), anti-osteoporosis agents, hormonereplacement therapies, oral contraceptives, anti-obesity agents,anti-anxiety agents, anti-proliferative agents, anti-tumor agents,anti-ulcer and gastroesophageal reflux disease agents, growth hormoneand/or growth hormone secretagogues, thyroid mimetics (including thyroidreceptor antagonist), anti-infective agents, anti-viral agents,anti-bacterial agents, and anti-fungal agents.

Other anticoagulant agents (or coagulation inhibitory agents) that maybe used in combination with the compounds of this invention includewarfarin and heparin (either unfractionated heparin or any commerciallyavailable low molecular weight heparin, for example LOVENOX™), syntheticpentasaccharide, direct acting thrombin inhibitors including hirudin andargatrobanas, factor VIIa, IXa, XIa inhibitors, well as other factor Xainhibitors such as those described in the publications identified aboveunder Background of the Invention.

The term anti-platelet agents (or platelet inhibitory agents), as usedherein, denotes agents that inhibit platelet function, for example byinhibiting the aggregation, adhesion or granular secretion of platelets.Agents include, but are not limited to, the various known non-steroidalanti-inflammatory drugs (NSAIDS) such as aspirin, ibuprofen, naproxen,sulindac, indomethacin, mefenamate, droxicam, diclofenac,sulfinpyrazone, piroxicam, and pharmaceutically acceptable salts orprodrugs thereof. Of the NSAIDS, aspirin (acetylsalicyclic acid or ASA)and piroxicam are preferred. Other suitable platelet inhibitory agentsinclude IIb/IIIa antagonists (e.g., tirofiban, eptifibatide, andabciximab), thromboxane-A2-receptor antagonists (e.g., ifetroban),thromboxane-A2-synthetase inhibitors, phosphodiesterase-III (PDE-III)inhibitors (e.g., dipyridamole, cilostazol), and PDE V inhibitors (suchas sildenafil), and pharmaceutically acceptable salts or prodrugsthereof.

The term anti-platelet agents (or platelet inhibitory agents), as usedherein, is also intended to include ADP (adenosine diphosphate) receptorantagonists, preferably antagonists of the purinergic receptors P₂Y₁ andP₂Y₁₂, with P₂Y₁₂ being even more preferred. Preferred P₂Y₁₂ receptorantagonists include ticlopidine and clopidogrel, includingpharmaceutically acceptable salts or prodrugs thereof. Clopidogrel is aneven more preferred agent. Ticlopidine and clopidogrel are alsopreferred compounds since they are known to be gentle on thegastro-intestinal tract in use.

The term thrombin inhibitors (or anti-thrombin agents), as used herein,denotes inhibitors of the serine protease thrombin. By inhibitingthrombin, various thrombin-mediated processes, such as thrombin-mediatedplatelet activation (that is, for example, the aggregation of platelets,and/or the granular secretion of plasminogen activator inhibitor-1and/or serotonin) and/or fibrin formation are disrupted. A number ofthrombin inhibitors are known to one of skill in the art and theseinhibitors are contemplated to be used in combination with the presentcompounds. Such inhibitors include, but are not limited to, boroargininederivatives, boropeptides, heparins, hirudin, argatroban, andmelagatran, including pharmaceutically acceptable salts and prodrugsthereof. Boroarginine derivatives and boropeptides include N-acetyl andpeptide derivatives of boronic acid, such as C-terminal α-aminoboronicacid derivatives of lysine, ornithine, arginine, homoarginine andcorresponding isothiouronium analogs thereof. The term hirudin, as usedherein, includes suitable derivatives or analogs of hirudin, referred toherein as hirulogs, such as disulfatohirudin. The term thrombolytics orfibrinolytic agents (or thrombolytics or fibrinolytics), as used herein,denote agents that lyse blood clots (thrombi). Such agents includetissue plasminogen activator (TPA, natural or recombinant) and modifiedforms thereof, anistreplase, urokinase, streptokinase, tenecteplase(TNK), lanoteplase (nPA), factor VIIa inhibitors, PAI-1 inhibitors(i.e., inactivators of tissue plasminogen activator inhibitors),alpha2-antiplasmin inhibitors, and anisoylated plasminogen streptokinaseactivator complex, including pharmaceutically acceptable salts orprodrugs thereof. The term anistreplase, as used herein, refers toanisoylated plasminogen streptokinase activator complex, as described,for example, in EP 028,489, the disclosure of which is herebyincorporated herein by reference herein. The term urokinase, as usedherein, is intended to denote both dual and single chain urokinase, thelatter also being referred to herein as prourokinase.

Examples of suitable anti-arrythmic agents for use in combination withthe present compounds include: Class I agents (such as propafenone);Class II agents (such as carvadiol and propranolol); Class III agents(such as sotalol, dofetilide, amiodarone, azimilide and ibutilide);Class IV agents (such as ditiazem and verapamil); K⁺ channel openerssuch as I_(Ach) inhibitors, and I_(Kur) inhibitors (e.g., compounds suchas those disclosed in WO01/40231).

Examples of suitable anti-hypertensive agents for use in combinationwith the compounds of the present invention include: alpha adrenergicblockers; beta adrenergic blockers; calcium channel blockers (e.g.,diltiazem, verapamil, nifedipine, amlodipine and mybefradil); diruetics(e.g., chlorothiazide, hydrochlorothiazide, flumethiazide,hydroflumethiazide, bendroflumethiazide, methylchlorothiazide,trichloromethiazide, polythiazide, benzthiazide, ethacrynic acidtricrynafen, chlorthalidone, furosemide, musolimine, bumetanide,triamtrenene, amiloride, spironolactone); renin inhibitors; ACEinhibitors (e.g., captopril, zofenopril, fosinopril, enalapril,ceranopril, cilazopril, delapril, pentopril, quinapril, ramipril,lisinopril); AT-1 receptor antagonists (e.g., losartan, irbesartan,valsartan); ET receptor antagonists (e.g., sitaxsentan, atrsentan andcompounds disclosed in U.S. Pat. Nos. 5,612,359 and 6,043,265); DualET/AII antagonist (e.g., compounds disclosed in WO 00/01389); neutralendopeptidase (NEP) inhibitors; vasopepsidase inhibitors (dual NEP-ACEinhibitors) (e.g., omapatrilat, gemopatrilat and nitrates); andβ-blockers (e.g., propanolol, nadolo, or carvedilol).

Examples of suitable cardiac glycosides for use in combination with thecompounds of the present invention include digitalis and ouabain.

Examples of suitable mineralocorticoid receptor antagonists for use incombination with the compounds of the present invention includesprionolactone and eplirinone.

Examples of suitable cholesterol/lipid lowering agents and lipid profiletherapies for use in combination with the compounds of the presentinvention include: HMG-CoA reductase inhibitors (e.g., pravastatin,lovastatin, atorvastatin, simvastatin, fluvastatin, NK-104 (a.k.a.itavastatin, or nisvastatin or nisbastatin) and ZD-4522 (a.k.a.rosuvastatin, or atavastatin or visastatin)); squalene synthetaseinhibitors; fibrates; bile acid sequestrants (such as questran); ACATinhibitors; MTP inhibitors; lipooxygenase inhibitors; choesterolabsorption inhibitors; and cholesterol ester transfer protein inhibitors(e.g., CP-529414).

Examples of suitable anti-diabetic agents for use in combination withthe compounds of the present invention include: biguanides (e.g.,metformin); glucosidase inhibitors (e.g., acarbose); insulins (includinginsulin secretagogues or insulin sensitizers); meglitinides (e.g.,repaglinide); sulfonylureas (e.g., glimepiride, glyburide andglipizide); biguanide/glyburide combinations (e.g., glucovance),thiozolidinediones (e.g., troglitazone, rosiglitazone and pioglitazone),PPAR-alpha agonists, PPAR-gamma agonists, PPAR alpha/gamma dualagonists, SGLT2 inhibitors, inhibitors of fatty acid binding protein(aP2) such as those disclosed in WO00/59506, glucagon-like peptide-1(GLP-1), and dipeptidyl peptidase IV (DP4) inhibitors.

Examples of suitable anti-depressant agents for use in combination withthe compounds of the present invention include nefazodone andsertraline.

Examples of suitable anti-inflammatory agents for use in combinationwith the compounds of the present invention include: prednisone;dexamethasone; enbrel; protien tyrosine kinase (PTK) inhibitors;cyclooxygenase inhibitors (including NSAIDs, and COX-1 and/or COX-2inhibitors); aspirin; indomethacin; ibuprofen; prioxicam; naproxen;celecoxib; and/or rofecoxib.

Examples of suitable anti-osteoporosis agents for use in combinationwith the compounds of the present invention include alendronate andraloxifene.

Examples of suitable hormone replacement therapies for use incombination with the compounds of the present invention include estrogen(e.g., congugated estrogens) and estradiol.

Examples of suitable anti-coagulants for use in combination with thecompounds of the present invention include heparins (e.g., unfractionedand low molecular weight heparins such as enoxaparin and dalteparin).

Examples of suitable anti-obesity agents for use in combination with thecompounds of the present invention include orlistat and aP2 inhibitors(such as those disclosed in WO00/59506).

Examples of suitable anti-anxiety agents for use in combination with thecompounds of the present invention include diazepam, lorazepam,buspirone, and hydroxyzine pamoate.

Examples of suitable anti-proliferative agents for use in combinationwith the compounds of the present invention include cyclosporin A,paclitaxel, adriamycin; epithilones, cisplatin, and carboplatin.

Examples of suitable anti-ulcer and gastroesophageal reflux diseaseagents for use in combination with the compounds of the presentinvention include famotidine, ranitidine, and omeprazole.

Administration of the compounds of the present invention (i.e., a firsttherapeutic agent) in combination with at least one additionaltherapeutic agent (i.e., a second therapeutic agent), preferably affordsan efficacy advantage over the compounds and agents alone, preferablywhile permitting the use of lower doses of each (i.e., a synergisticcombination). A lower dosage minimizes the potential of side effects,thereby providing an increased margin of safety. It is preferred that atleast one of the therapeutic agents is administered in a sub-therapeuticdose. It is even more preferred that all of the therapeutic agents beadministered in sub-therapeutic doses. Sub-therapeutic is intended tomean an amount of a therapeutic agent that by itself does not give thedesired therapeutic effect for the condition or disease being treated.Synergistic combination is intended to mean that the observed effect ofthe combination is greater than the sum of the individual agentsadministered alone.

The compounds of the present invention are also useful as standard orreference compounds, for example as a quality standard or control, intests or assays involving the inhibition of factor Xa. Such compoundsmay be provided in a commercial kit, for example, for use inpharmaceutical research involving factor Xa. For example, a compound ofthe present invention could be used as a reference in an assay tocompare its known activity to a compound with an unknown activity. Thiswould ensure the experimenter that the assay was being performedproperly and provide a basis for comparison, especially if the testcompound was a derivative of the reference compound. When developing newassays or protocols, compounds according to the present invention couldbe used to test their effectiveness.

The compounds of the present invention may also be used in diagnosticassays involving factor Xa. For example, the presence of factor Xa in anunknown sample could be determined by addition of chromogenic substrateS2222 to a series of solutions containing test sample and optionally oneof the compounds of the present invention. If production of pNA isobserved in the solutions containing test sample, but not in thepresence of a compound of the present invention, then one would concludefactor Xa was present.

Compounds of the present invention may further be useful as diagnosticagents and adjuncts. For example, the present compounds may be useful inmaintaining whole and fractionated blood in the fluid phase such asrequired for analytical and biological testing.

The present invention also encompasses an article of manufacture. Asused herein, article of manufacture is intended to include, but not belimited to, kits and packages. The article of manufacture of the presentinvention, comprises: (a) a first container; (b) a pharmaceuticalcomposition located within the first container, wherein the composition,comprises: a first therapeutic agent, comprising: a compound of thepresent invention or a pharmaceutically acceptable salt form thereof;and, (c) a package insert stating that the pharmaceutical compositioncan be used for the treatment of a thromboembolic disorder (as definedpreviously). In another embodiment, the package insert states that thepharmaceutical composition can be used in combination (as definedpreviously) with a second therapeutic agent to treat a thromboembolicdisorder. The article of manufacture can further comprise: (d) a secondcontainer, wherein components (a) and (b) are located within the secondcontainer and component (c) is located within or outside of the secondcontainer. Located within the first and second containers means that therespective container holds the item within its boundaries.

The first container is a receptacle used to hold a pharmaceuticalcomposition. This container can be for manufacturing, storing, shipping,and/or individual/bulk selling. First container is intended to cover abottle, jar, vial, flask, syringe, tube (e.g., for a cream preparation),or any other container used to manufacture, hold, store, or distribute apharmaceutical product.

The second container is one used to hold the first container and,optionally, the package insert. Examples of the second containerinclude, but are not limited to, boxes (e.g., cardboard or plastic),crates, cartons, bags (e.g., paper or plastic bags), pouches, and sacks.The package insert can be physically attached to the outside of thefirst container via tape, glue, staple, or another method of attachment,or it can rest inside the second container without any physical means ofattachment to the first container. Alternatively, the package insert islocated on the outside of the second container. When located on theoutside of the second container, it is preferable that the packageinsert is physically attached via tape, glue, staple, or another methodof attachment. Alternatively, it can be adjacent to or touching theoutside of the second container without being physically attached.

The package insert is a label, tag, marker, etc. that recitesinformation relating to the pharmaceutical composition located withinthe first container. The information recited will usually be determinedby the regulatory agency governing the area in which the article ofmanufacture is to be sold (e.g., the United States Food and DrugAdministration). Preferably, the package insert specifically recites theindications for which the pharmaceutical composition has been approved.The package insert may be made of any material on which a person canread information contained therein or thereon. Preferably, the packageinsert is a printable material (e.g., paper, plastic, cardboard, foil,adhesive-backed paper or plastic, etc.) on which the desired informationhas been formed (e.g., printed or applied).

Dosage and Formulation

The compounds of this invention can be administered in such oral dosageforms as tablets, capsules (each of which includes sustained release ortimed release formulations), pills, powders, granules, elixirs,tinctures, suspensions, syrups, and emulsions. They may also beadministered in intravenous (bolus or infusion), intraperitoneal,subcutaneous, or intramuscular form, all using dosage forms well knownto those of ordinary skill in the pharmaceutical arts. They can beadministered alone, but generally will be administered with apharmaceutical carrier selected on the basis of the chosen route ofadministration and standard pharmaceutical practice.

The dosage regimen for the compounds of the present invention will, ofcourse, vary depending upon known factors, such as the pharmacodynamiccharacteristics of the particular agent and its mode and route ofadministration; the species, age, sex, health, medical condition, andweight of the recipient; the nature and extent of the symptoms; the kindof concurrent treatment; the frequency of treatment; the route ofadministration, the renal and hepatic function of the patient, and theeffect desired. A physician or veterinarian can determine and prescribethe effective amount of the drug required to prevent, counter, or arrestthe progress of the thromboembolic disorder.

By way of general guidance, the daily oral dosage of each activeingredient, when used for the indicated effects, will range betweenabout 0.001 to 1000 mg/kg of body weight, preferably between about 0.01to 100 mg/kg of body weight per day, and most preferably between about1.0 to 20 mg/kg/day. Intravenously, the most preferred doses will rangefrom about 1 to about 10 mg/kg/min during a constant rate infusion.Compounds of this invention may be administered in a single daily dose,or the total daily dosage may be administered in divided doses of two,three, or four times daily.

Compounds of this invention can be administered in intranasal form viatopical use of suitable intranasal vehicles, or via transdermal routes,using transdermal skin patches. When administered in the form of atransdermal delivery system, the dosage administration will, of course,be continuous rather than intermittent throughout the dosage regimen.

The compounds are typically administered in admixture with suitablepharmaceutical diluents, excipients, or carriers (collectively referredto herein as pharmaceutical carriers) suitably selected with respect tothe intended form of administration, that is, oral tablets, capsules,elixirs, syrups and the like, and consistent with conventionalpharmaceutical practices.

For instance, for oral administration in the form of a tablet orcapsule, the active drug component can be combined with an oral,non-toxic, pharmaceutically acceptable, inert carrier such as lactose,starch, sucrose, glucose, methyl cellulose, magnesium stearate,dicalcium phosphate, calcium sulfate, mannitol, sorbitol and the like;for oral administration in liquid form, the oral drug components can becombined with any oral, non-toxic, pharmaceutically acceptable inertcarrier such as ethanol, glycerol, water, and the like. Moreover, whendesired or necessary, suitable binders, lubricants, disintegratingagents, and coloring agents can also be incorporated into the mixture.Suitable binders include starch, gelatin, natural sugars such as glucoseor beta-lactose, corn sweeteners, natural and synthetic gums such asacacia, tragacanth, or sodium alginate, carboxymethylcellulose,polyethylene glycol, waxes, and the like. Lubricants used in thesedosage forms include sodium oleate, sodium stearate, magnesium stearate,sodium benzoate, sodium acetate, sodium chloride, and the like.Disintegrators include, without limitation, starch, methyl cellulose,agar, bentonite, xanthan gum, and the like.

The compounds of the present invention can also be administered in theform of liposome delivery systems, such as small unilamellar vesicles,large unilamellar vesicles, and multilamellar vesicles. Liposomes can beformed from a variety of phospholipids, such as cholesterol,stearylamine, or phosphatidylcholines.

Compounds of the present invention may also be coupled with solublepolymers as targetable drug carriers. Such polymers can includepolyvinylpyrrolidone, pyran copolymer,polyhydroxypropylmethacrylamide-phenol,polyhydroxyethylaspartamidephenol, or polyethyleneoxide-polylysinesubstituted with palmitoyl residues. Furthermore, the compounds of thepresent invention may be coupled to a class of biodegradable polymersuseful in achieving controlled release of a drug, for example,polylactic acid, polyglycolic acid, copolymers of polylactic andpolyglycolic acid, polyepsilon caprolactone, polyhydroxy butyric acid,polyorthoesters, polyacetals, polydihydropyrans, polycyanoacylates, andcrosslinked or amphipathic block copolymers of hydrogels.

Dosage forms (pharmaceutical compositions) suitable for administrationmay contain from about 1 milligram to about 100 milligrams of activeingredient per dosage unit. In these pharmaceutical compositions theactive ingredient will ordinarily be present in an amount of about0.5-95% by weight based on the total weight of the composition.

Gelatin capsules may contain the active ingredient and powderedcarriers, such as lactose, starch, cellulose derivatives, magnesiumstearate, stearic acid, and the like. Similar diluents can be used tomake compressed tablets. Both tablets and capsules can be manufacturedas sustained release products to provide for continuous release ofmedication over a period of hours. Compressed tablets can be sugarcoated or film coated to mask any unpleasant taste and protect thetablet from the atmosphere, or enteric coated for selectivedisintegration in the gastrointestinal tract.

Liquid-dosage forms for oral administration can contain coloring andflavoring to increase patient acceptance.

In general, water, a suitable oil, saline, aqueous dextrose (glucose),and related sugar solutions and glycols such as propylene glycol orpolyethylene glycols are suitable carriers for parenteral solutions.Solutions for parenteral administration preferably contain a watersoluble salt of the active ingredient, suitable stabilizing agents, andif necessary, buffer substances. Antioxidizing agents such as sodiumbisulfite, sodium sulfite, or ascorbic acid, either alone or combined,are suitable stabilizing agents. Also used are citric acid and its saltsand sodium EDTA. In addition, parenteral solutions can containpreservatives, such as benzalkonium chloride, methyl- or propyl-paraben,and chlorobutanol.

Suitable pharmaceutical carriers are described in Remington'sPharmaceutical Sciences, 18th ed., Mack Publishing Company, Easton, Pa.,1990, a standard reference text in this field.

Where the compounds of this invention are combined with otheranticoagulant agents, for example, a daily dosage may be about 0.1 to100 milligrams of the compound of The present invention and about 1 to7.5 milligrams of the second anticoagulant, per kilogram of patient bodyweight. For a tablet dosage form, the compounds of this inventiongenerally may be present in an amount of about 5 to 10 milligrams perdosage unit, and the second anti-coagulant in an amount of about 1 to 5milligrams per dosage unit.

Where the compounds of the present invention are administered incombination with an anti-platelet agent, by way of general guidance,typically a daily dosage may be about 0.01 to 25 milligrams of thecompound of The present invention and about 50 to 150 milligrams of theanti-platelet agent, preferably about 0.1 to 1 milligrams of thecompound of The present invention and about 1 to 3 milligrams ofantiplatelet agents, per kilogram of patient body weight.

Where the compounds of The present invention are administered incombination with thrombolytic agent, typically a daily dosage may beabout 0.1 to 1 milligrams of the compound of The present invention, perkilogram of patient body weight and, in the case of the thrombolyticagents, the usual dosage of the thrombolyic agent when administeredalone may be reduced by about 70-80% when administered with a compoundof The present invention.

Where two or more of the foregoing second therapeutic agents areadministered with the compound of The present invention, generally theamount of each component in a typical daily dosage and typical dosageform may be reduced relative to the usual dosage of the agent whenadministered alone, in view of the additive or synergistic effect of thetherapeutic agents when administered in combination.

Particularly when provided as a single dosage unit, the potential existsfor a chemical interaction between the combined active ingredients. Forthis reason, when the compound of The present invention and a secondtherapeutic agent are combined in a single dosage unit they areformulated such that although the active ingredients are combined in asingle dosage unit, the physical contact between the active ingredientsis minimized (that is, reduced). For example, one active ingredient maybe enteric coated. By enteric coating one of the active ingredients, itis possible not only to minimize the contact between the combined activeingredients, but also, it is possible to control the release of one ofthese components in the gastrointestinal tract such that one of thesecomponents is not released in the stomach but rather is released in theintestines. One of the active ingredients may also be coated with amaterial that affects a sustained-release throughout thegastrointestinal tract and also serves to minimize physical contactbetween the combined active ingredients. Furthermore, thesustained-released component can be additionally enteric coated suchthat the release of this component occurs only in the intestine. Stillanother approach would involve the formulation of a combination productin which the one component is coated with a sustained and/or entericrelease polymer, and the other component is also coated with a polymersuch as a low viscosity grade of hydroxypropyl methylcellulose (HPMC) orother appropriate materials as known in the art, in order to furtherseparate the active components. The polymer coating serves to form anadditional barrier to interaction with the other component.

These as well as other ways of minimizing contact between the componentsof combination products of the present invention, whether administeredin a single dosage form or administered in separate forms but at thesame time by the same manner, will be readily apparent to those skilledin the art, once armed with the present disclosure.

Other features of the invention will become apparent in the course ofthe following descriptions of exemplary embodiments that are affordedfor illustration of the invention and are not intended to be limitingthereof.

EXAMPLES Example 12-[6-(2′-methanesulfonyl-biphenyl-4-yl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzamide

Part A: To a 0° C. solution of 5-methoxyanthranilic acid (5.0 g, 29.9mmol) in concentrated hydrochloric acid (10 mL) was added dropwise anice cold solution of sodium nitrite (2.06 g, 29.9 mmol) in water (5 mL)and stirring was continued at 0° C. for 30 minutes. Stannous chloridedihydrate (16.8 g, 74.8 mmol) was dissolved in concentrated hydrochloricacid (16 mL), cooled to 0° C., and added slowly to the solution of thediazonium salt. The precipitate was agitated, kept at 0° C. for 30minutes, and then filtered. The solids were washed successively with icecold brine and petroleum ether and dried under a stream of air and thenunder vacuum. The crude hydrazine salt and3-hydroxy-1-(4-iodo-phenyl)-4-(2,2,2-trifluoro-acetyl)-5,6-dihydro-1H-pyridin-2-one(12.3 g, 29.9 mmol) were combined in glacial acetic acid (50 mL) andheated to 80° C. Upon completion of the reaction the solvent wasevaporated to a viscous oil which was subjected to silica gel columnchromatography to yield2-[6-(4-iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzoicacid methyl ester (4.12 g, 24%). MS (AP+) 571.9 (100%).

Part B:2-[6-(4-Iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzoicacid methyl ester (2.00 g, 3.50 mmol), 2-(methylthio)phenylboronic acid(647 mg, 3.85 mmol), bis(triphenylphosphine)palladium(II) chloride (122mg, 0.175 mmol), tetrabutylammonium bromide (56 mg, 0.175 mmol), andsodium carbonate (1.11 g, 10.5 mmol) were combined, the flask purgedwith argon and degassed benzene (50 mL) and water (5 mL) were added. Theflask was heated to reflux for 14 h, cooled to ambient temperature, andpoured into ethyl acetate/water. The phases were separated and theaqueous phase extracted once with ethyl acetate. The organic phases werecombined, dried over sodium sulfate, filtered, and evaporated. The crude5-methoxy-2-[6-(2′-methylsulfanyl-biphenyl-4-yl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-benzoicacid methyl ester was dissolved in dichloromethane (50 mL) andmeta-chloroperbenzoic acid (2.41 g, 70%, 9.8 mmol) was added as a solid.Upon completion the reaction was poured into water (50 mL), and sodiumsulfite was added until the aqueous layer tested negative tostarch/potassium iodide paper. The phases were separated, and theorganic was washed once with sodium bicarbonate, dried over sodiumsulfate, filtered, and evaporated. The solid was subjected to silica gelcolumn chromatography to yield2-[6-(2′-methanesulfonyl-biphenyl-4-yl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzoicacid methyl ester (1.70 g, 81%) as a colorless solid. This material(1.69 g, 2.81 mmol) was stirred in dioxane (15 mL) and 10% sodiumhydroxide (15 mL). The reaction was acidified with concentratedhydrochloric acid to pH 3 and extracted with ethyl acetate (3×10 mL).The combined extracts were washed with water (5×10 mL), dried oversodium sulfate, filtered, and evaporated.2-[6-(2′-Methanesulfonyl-biphenyl-4-yl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzoicacid was isolated as a colorless solid in nearly quantitative yield.This material (59.2 mg, 0.101 mmol) was dissolved in dry chloroform (3mL) to which was added thionyl chloride (37 μL, 0.505 mmol), and thereaction heated to reflux. The solvent was evaporated, and the residuedried under vacuum to give2-[6-(2′-methanesulfonyl-biphenyl-4-yl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin1-yl]-5-methoxy-benzoyl chloride.

Part C:2-[6-(2′-Methanesulfonyl-biphenyl-4-yl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzoylchloride (0.10 mmol) was dissolved in dry dichloromethane (1 mL) under anitrogen atmosphere, and a stream of ammonia gas was introduced for 30sec. The solvent was evaporated, and the residue was purified by reversephase HPLC to give the title compound as a colorless solid. MS (ES+)607.1 (M+Na)⁺(100%); ¹H NMR (DMSO-d₆) δ 8.08 (d, 1H, J=6.6 Hz),7.79-7.34 (m, 10H), 7.16 (d, 1H, J=2.9 Hz), 7.09 (dd, 1H, J=8.5, 2.6),4.11 (t, 2H, J=6.4 Hz), 3.84 (s, 3H), 3.11 (t, 2H, J=6.4), 2.81 (s, 3H).

Example 22-[6-(2′-Methanesulfonyl-biphenyl-4-yl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-benzamide

The title compound was synthesized from 2-aminobenzoic acid methyl esterin an analogous manner to Example 1. MS (ES+) 555.1 (M+H)⁺(100%).

Examples 3-32

The compounds shown in Table 1 (examples 3-32) were prepared in ananalogous manner to Example 1 employing the general procedure (Example1, part C) and substituting the appropriate amine. TABLE 1 Ex. StructureMF MS:(M + H)⁺ 3

C₃₂H₃₂F₃N₅O₅S 656.2 4

C₃₃H₂₉F₃N₆O₅S 679.2 5

C₃₃H₂₆F₃N₅O₅S 662.2 6

C₃₄H₂₈F₃N₅O₅S 676.2 7

C₃₆H₃₂F₃N₅O₅S 704.2 8

C₃₀H₂₈F₃N₅O₅S 628.2 9

C₃₁H₃₀F₃N₅O₅S 642.2 10

C₃₅H₃₆F₃N₅O₅S 696.2 11

C₃₃H₃₂F₃N₅O₅S 668.2 12

C₃₁H₂₉F₃N₄O₆S 643.2 13

C₃₃H₂₆F₃N₅O₅S 662.2 14

C₃₃H₃₂F₃N₅O₅S 668.2 15

C₃₃H₃₄F₃N₅O₅S 670.2 16

C₃₄H₃₃F₃N₄O₆S 683.2 17

C₃₂H₂₉F₃N₄O₆S 655.2 18

C₃₆H₃₁F₃N₄O₆S 705.2 19

C₃₆H₃₁F₃N₄O₆S 705.2 20

C₃₂H₃₁F₃N₄O₇S 673.2 21

C₃₁H₂₉F₃N₄O₆S 643.2 22

C₃₁H₂₉F₃N₄O₆S 643.2 23

C₃₃H₃₁F₃N₄O₆S 669.2 24

C₃₆H₃₁F₃N₄O₆S 705.2 25

C₃₁H₂₉F₃N₄O₇S 659.2 26

C₃₀H₂₇F₃N₄O₆S 629.2 27

C₃₁H₂₉F₃N₄O₆S 643.2 28

C₃₃H₃₁F₃N₄O₆S 669.2 29

C₃₇H₃₁F₃N₄O₆S 717.2 30

C₃₄H₂₇F₃N₄O₆S 677.2 31

C₃₀H₂₇F₃N₄O₆S 629.2 32

C₃₂H₂₇F₃N₆O₅S 665.2

Example 335-Methoxy-N-[2-(1-methyl-pyrrolidin-2-yl)-ethyl]-2-{7-oxo-6-[4-(2-oxo-2H-pyridin-1-yl)phenyl]-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl}-benzamide,trifluoroacetic acid salt

The title compound was prepared from2-[6-(4-iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzoicacid methyl ester as obtained in Example 1. The ester (159 mg, 0.278mmol) was dissolved in ethylene glycol (2 mL) containing2-(1-methyl-pyrrolidin-2-yl)-ethylamine (400 μL, 2.78 mmol) and heatedto 85° C. for 12 h. The reaction was poured into water and extractedwith ethyl acetate (3×10 mL). The combined extracts were washed withwater (5×10 mL), dried over sodium sulfate, filtered, and evaporated.The residue was purified by preparative thin layer chromatography togive2-[6-(4-iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-N-[2-(1-methyl-pyrrolidin-2-yl)-ethyl]-benzamide(60 mg, 32%) as a faint yellow solid. MS (ES+) 668.4 (M+H)⁺(100%). Thismaterial (60 mg, 0.089 mmol) was combined with 2-pyridone (17 mg, 0.18mmol), anhydrous potassium carbonate (49 mg, 0.36 mmol), copper(I)iodide (3.4 mg, 0.018 mmol), 1,10-phenanthroline (3.2 mg, 0.018 mmol),and dry-degassed dimethylsulfoxide (1.0 mL) and heated to 140° C. for 6h. The mixture was cooled to ambient temperature and diluted with 6Nammonium hydroxide and ethyl acetate. The phases were separated, and theaqueous phase extracted once with ethyl acetate. The combined organicextracts were washed successively with water (2×) and 3N ammoniumhydroxide, dried over sodium sulfate, filtered, and evaporated. Theresidue was purified by preparative HPLC to give the title compound as acolorless solid. MS (ES+) 635.5 (M+H)⁺(100%).

Example 342-[6-(4-Iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-N-pyridin-3-yl-benzamide

The title compound was prepared from2-[6-(4-iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzoicacid methyl ester as obtained in Example 1. The ester (270 mg, 0.47mmol) was stirred in tetrahydrofuran (1 mL) and 10% sodium hydroxide (1mL) for 5 h. The reaction was acidified with 1N hydrochloric acid to pH3 and extracted with ethyl acetate (3×5 mL). The combined extracts werewashed with water (2×5 mL), dried over sodium sulfate, filtered, andevaporated to give2-[6-(4-iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzoicacid (263 mg, 100%) as a colorless solid. The acid (263 mg, 0.47 mmol)was dissolved in dimethylformamide (3 mL) to which were addedtriethylamine (233 mL, 1.68 mmol) and 3-aminopyridine (54 mg, 0.58mmol). After 10 minutesbenzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate(BOP reagent) was added and stirring continued for 24 hr. The reactionwas poured into ethyl acetate/water, and the phases were separated. Theaqueous was extracted twice with ethyl acetate. The combined organicswere washed with water (4×) and once with brine, dried over sodiumsulfate, filtered, and evaporated to give 278 mg (91%) of a light orangecolored solid. The material was purified by preparative HPLC to give thetitle compound as a colorless solid. MS (ES+) 634.0 (M+H)⁺(100%).

Example 355-Methoxy-2-(7-oxo-6-phenyl-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl)-N-pyridin-3-yl-benzamide

2-[6-(4-Iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-N-pyridin-3-yl-benzamide(15 mg, 0.023 mmol) was combined with 5% palladium on carbon and stirredin ethanol under 1 atmosphere of hydrogen for 12 h. The reaction mixturewas filtered through diatomaceous earth and the solvent evaporated togive the title compound (11 mg, 95%) as a colorless solid. MS (ES+)508.0 (M+H)⁺(100%).

Example 36N-(1H-Imidazol-2-ylmethyl)-2-[6-(4-iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzamide,bis-trifluoroacetic acid salt

2-[6-(4-Iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzoicacid (186 mg, 0.334 mmol) was dissolved in dry chloroform (10 mL) towhich was added thionyl chloride (243 μL, 3.34 mmol), and the reactionheated to reflux. The solvent was evaporated, and the residue driedunder vacuum to give2-[6-(4-iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzoylchloride as a pale yellow foam. This material was dissolved in drymethylene chloride (10 mL) to which were added pyridine (0.14 mL, 1.67mmol), N,N-dimethylaminopyridine (4 mg, 0.033 mmol), and lastlyC-(1H-imidazol-2-yl)-methylamine bis-hydrochloride (114 mg, 0.668 mmol).Upon completion of the reaction the solvent was evaporated, and theresidue was purified by preparative HPLC to give the title compound (69mg, 24%) as a colorless solid. MS (ES+) 636.9 (M+H)⁺(100%).

Examples 37-45

The compounds shown in Table 2 (examples 37-45) were prepared in ananalogous manner to Example 1 employing the general procedure (Example1, part C) and substituting the appropriate amine. TABLE 2 Ex. StructureMF (M + H)⁺ 37

C₂₆H₃₁N₅O₆S 542.2 38

C₂₅H₂₉N₅O₆S 528.2 39

C₂₈H₂₈N₆O₅S 561.2 40

C₂₈H₂₈N₆O₅S 561.2 41

C₂₈H₂₈N₆O₅S 561.2 42

C₂₆H₃₁N₅O₆S 542.2 43

C₂₆H₃₁N₅O₆S 542.2 44

C₂₇H₂₉N₇O₅S 564.2 45

C₂₃H₂₅N₅O₅S 484.2

Example 462-[6-(4-Chloro-phenyl)-3-methyl-7-oxo-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzenesulfonamide

(2-[6-(4-Chloro-phenyl)-3-methyl-7-oxo-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzenesulfonicacid is synthesized from anisidine-2-sulfonic acid in an analogousmanner as described in Example 1.

Examples 47-61

The compounds shown in Table 3 (examples 47-61) were prepared inanalogous manner to Example 46 employing the general procedure(example 1) and methods described in WO 03/26652 and substituting theappropriate amine. TABLE 3 Ex. Structure MF (M + H)⁺ 47

C₂₇H₂₃F₃N₄O₆ 621.1 48

C₂₇H₂₃F₃N₄O₄S₂ 589.1 49

C₂₆H₂₆F₃N₇O₄S 590.2 50

C₂₄H₂₁F₃N₆O₄S 547.1 51

C₂₄H₁₈F₃N₅O₄S 530.1 52

C₂₅H₂₄F₃N₇O₃S 560.2 53

C₂₇H₂₄F₃N₅O₃S 556.2 54

C₂₈H₂₆F₃N₅O₃S 570.2 55

C₃₀H₂₈F₃N₅O₄S 612.2 56

C₃₁H₃₀F₃N₅O₄S 626.2 57

C₂₆H₂₁F₃N₄O₃S₂ 559.1 58

C₁₉H₁₄F₃IN₄O₃S 563.0 59

C₂₆H₂₁F₃N₄O₅S₂ 591.1 60

C₂₄H₂₂F₃N₅O₄S 534.1 61

C₂₆H₂₀F₃N₅O₅S 572.1

Examples 62-106

The compounds shown in Table 4 (examples 62-106) were prepared accordingto the general procedure described below.

Part A: Preparation of2-(5-furan-2-yl-3-trifluoromethyl-pyrazol-1-yl)-5-methoxy-benzoic acidmethyl ester. To a solution of 2-amino-5-methoxy-benzoic acid methylester hydrochloride (201 mg, 0.922 mmol) in 1N hydrochloric acid (6 mL)cooled to 0° C. was added dropwise an ice cold solution of sodiumnitrite (68 mg, 0.992 mmol) in water (1 mL). The solution was stirred at0° C. for 45 minutes after which an ice cold solution of stannouschloride dihydrate (520 mg, 2.30 mmol) in 1N hydrochloric acid (2 mL)was added dropwise and stirred rapidly for an additional 15 min. at 0°C. A solution of 4,4,4-trifluoro-1-furan-2-yl-butane-1,3-dione inmethanol (2 mL) was added, the cooling bath removed, and the reactionallowed to warm to ambient temperature. The solution was heated to 50°C. for 15 h and upon completion of the reaction the solvent volume wasreduced under reduced pressure. Ethyl acetate was added, and the phaseswere separated. The aqueous layer was extracted once with ethyl acetate,and the combined organics were washed once with water, brine, dried oversodium sulfate, filtered, and evaporated to give 270 mg (80%) of2-(5-furan-2-yl-3-trifluoromethyl-pyrazol-1-yl)-5-methoxy-benzoic acidmethyl ester.

Part B: Preparation of2-(4-methoxy-2-methoxycarbonyl-phenyl)-5-trifluoromethyl-2H-pyrazole-3-carboxylicacid. A solution2-(5-furan-2-yl-3-trifluoromethyl-pyrazol-1-yl)-5-methoxy-benzoic acidmethyl ester (1.00 g, 2.73 mmol) in acetonitrile (9 mL) was added to asolution of sodium dihydrogenphosphate (1.63 g, 13.6 mmol) in water (2mL) cooled to 0° C. To this mixture was added, using an addition funnel,a solution of sodium chlorite (3.1 g, 80%, 27.3 mmol) in water (9 mL) inthree equal portions with ten minutes between each addition. Thereaction was allowed to warm to ambient temperature and stirred for 14h. Upon completion of the reaction, a solution of 1N sodium hydroxide(10 mL) was added, and the mixture was extracted with chloroform (2×25mL). The combined chloroform extracts were extracted with saturatedsodium bicarbonate. The combined basic layers were made acidic (pH 2.0)with concentrated hydrochloric acid and extracted twice with ethylacetate, dried over magnesium sulfate, and evaporated to give 348 mg(37%) of2-(4-methoxy-2-methoxycarbonyl-phenyl)-5-trifluoromethyl-2H-pyrazole-3-carboxylicacid.

Part C: Preparation of2-[5-(3-Fluoro-2′-methanesulfonyl-biphenyl-4-ylcarbamoyl)-3-trifluoromethyl-pyrazol-1-yl]-5-methoxy-benzoicacid methyl ester. 3-Fluoro-2′-methanesulfonyl-biphenyl-4-ylamine (231mg, 0.87 mmol) and2-(4-methoxy-2-methoxycarbonyl-phenyl)-5-trifluoromethyl-2H-pyrazole-3-carboxylicacid (300 mg, 0.87 mmol) were combined in a flask and placed under anitrogen atmosphere. Pyridine (4.0 mL) was added, and the flask wascooled to −15° C. After stirring for five minutes, phosphorousoxychloride (97 μL, 1.04 mmol) was added dropwise followed by additionalstirring for one hour while maintaining a reaction temperature of −10 to−15° C. The reaction was diluted with dichloromethane, washed with 0.1 Mhydrochloric acid (3×), dried over magnesium sulfate, filtered,evaporated under reduced pressure, and dried under high vacuum for 12 h.2-[5-(3-Fluoro-2′-methanesulfonyl-biphenyl-4-ylcarbamoyl)-3-trifluoromethyl-pyrazol-1-yl]-5-methoxy-benzoicacid methyl ester (514 mg, 84%) was isolated in sufficient purity to beused in the next step.

Part D: Preparation of2-[5-(3-Fluoro-2′-methanesulfonyl-biphenyl-4-ylcarbamoyl)-3-trifluoromethyl-pyrazol-1-yl]-5-methoxy-benzoicacid.2-[5-(3-Fluoro-2′-methanesulfonyl-biphenyl-4-ylcarbamoyl)-3-trifluoromethyl-pyrazol-1-yl]-5-methoxybenzoicacid methyl ester (1.70 g, 2.80 mmol) was dissolved in methanol (22 mL),1N sodium hydroxide (5.8 mL) was added, and the solution refluxed for 6hours. The reaction was cooled to ambient temperature and diluted withwater (30 mL). 3N hydrochloric acid was added to adjust the pH to 2, andthe resulting precipitate collected by filtration. The solid was driedunder vacuum in a desiccator to give 1.45 g (86%) of(3-fluoro-2′-methanesulfonyl-biphenyl-4-ylcarbamoyl)-3-trifluoromethyl-pyrazol-1-yl]-5-methoxy-benzoicacid. ¹H NMR (CD₃OD) δ 8.12 (dd, J=1.5, 8.1 Hz, 1H), 7.86 (t, J=8.4 Hz,1H), 7.70 (dt, J=1.5, 7.7 Hz, 1H), 7.61 (dt, J=1.5, 7.7 Hz, 1H), 7.37(m, 3H), 7.25 (dd, J=2.2, 11.7 Hz, 1H) 7.16 (m, 3H) 3.87 (s, 3H), 2.67(s, 3H).

Part E: Preparation of tert-Butoxycarbonylamino-N-alkylcarboxamides:tert-Butoxycarbonylamino-carboxylic acid (0.50 mmol) was dissolved inN,N-dimethylformamide (6.0 mL); 1-hydroxybenzotriazole (132 mg, 0.98mmol) was added and the solution was stirred at ambient temperature for30 minutes. 1,3-Diisopropylcarbodiimide (153 mg, 0.98 mmol) and amine(0.50 mmol) were added and stirring continued for 12 h at ambienttemperature. PS-Trisamine (592 mg, 2.0 mmol) was added and stirringcontinued for three hours, after which the reaction was filtered and thesolvent evaporated. To the residue was added trifluoroaceticacid/dichloromethane (1:1)(1.5 mL), stirring was continued for 30minutes, and the solvent was evaporated under reduced pressure, yieldinga nearly quantitative yield (crude) of a yellow-orange amorphous solid.

To a portion of the carboxylic acid 3 (0.134 mmol) was addeddimethylformamide (1.0 mL) followed by 1-hydroxybenzotriazole (21 mg,0.134 mmol) and 1,3-diisopropylcarbodiimide (17 mg, 0.134 mmol), whichwas then stirred for 30 minutes at ambient temperature.2-[5-3-Fluoro-2′-methanesulfonyl-biphenyl-4-ylcarbamoyl)-3-trifluoromethyl-pyrazol-1-yl]-5-methoxybenzoicacid (20 mg, 0.067 mmol) and N,N-diisopropylethylamine (35 μL, 0.201mmol) were added and stirring was continued at ambient temperature for12 h. The solvent was evaporated under reduced pressure and the residuepurified by reverse phase HPLC, collecting products using amass-directed trigger. TABLE 4 MS:(M + Ex. Structure MF H)⁺ 62

C₃₆H₃₁F₄N₅O₆S 738.2 63

C₃₇H₃₃F₄N₅O₆S 752.2 64

C₃₆H₃₀ClF₄N₅O₆S 772.2 65

C₃₇H₃₂ClF₄N₅O₆S 786.2 66

C₃₆H₃₀ClF₄N₅O₆S 772.2 67

C₃₆H₂₉F₄N₅O₈S 768.2 68

C₃₈H₃₃F₄N₅O₈S 796.2 69

C₃₇H₃₁F₄N₅O₈S 782.2 70

C₃₉H₃₆F₄N₆O₈S 825.2 71

C₃₇H₃₁F₄N₅O₉S 798.2 72

C₄₃H₃₅F₄N₅O₈S 858.2 73

C₃₄H₃₄F₄N₆O₇S 747.2 74

C₃₅H₃₆F₄N₆O₇S 761.2 75

C₃₆H₃₈F₄N₆O₇S 775.3 76

C₃₅H₂₉F₄N₅O₆S 724.2 77

C₃₈H₃₆F₄N₆O₆S 781.2 78

C₄₂H₃₅F₄N₅O₆S 814.2 79

C₃₅H₂₈ClF₄N₅O₆S 758.1 80

C₃₇H₃₀ClF₄N₅O₈S 816.2 81

C₃₈H₃₅ClF₄N₆O₆S 815.2 82

C₃₆H₃₀ClF₄N₅O₇S 788.2 83

C₄₂H₃₄ClF₄N₅O₆S 848.2 84

C₃₈H₃₅F₄N₅O₇S 782.2 85

C₃₂H₃₀F₄N₆O₇S 719.2 86

C₃₃H₃₂F₄N₆O₇S 733.2 87

C₃₄H₃₄F₄N₆O₇S 747.2 88

C₃₁H₂₉F₄N₅O₇S 692.2 89

C₃₂H₃₁F₄N₅O₇S 706.2 90

C₃₃H₃₃F₄N₅O₇S 720.2 91

C₃₆H₃₁F₄N₅O₆S 738.2 92

C₃₇H₃₃F₄N₅O₆S 752.2 93

C₃₈H₃₅F₄N₅O₆S 766.2 94

C₃₉H₃₈F₄N₆O₆S 795.3 95

C₃₇H₃₃F₄N₅O₇S 768.2 96

C₄₃H₃₇F₄N₅O₆S 828.2 97

C₃₁H₂₉F₄N₅O₆S 676.2 98

C₃₂H₃₁F₄N₅O₆S 690.2 99

C₃₂H₃₁F₄N₅O₆S 690.2 100

C₃₃H₃₁F₄N₅O₈S 734.2 101

C₃₄H₃₆F₄N₆O₆S 733.2 102

C₃₂H₃₁F₄N₅O₇S 706.2 103

C₂₆H₂₀F₄N₄O₅S 577.1 104

C₃₃H₂₆F₄N₄O₅S 667.2 105

C₄₅H₄₈F₄N₆O₉S 925.3 106

C₄₂H₄₃F₄N₅O₉S 870.3

Example 1072-(2-Carbamoyl-4-methoxy-phenyl)-5-trifluoromethyl-2H-pyrazole-3-carboxylicacid (4-dimethylamino-phenyl)-amide

The title compound was prepared in a analogous manner to the generalprocedure for examples 62-106. C₂₁H₂₀F₃N₅O₃. MS:(M+H)⁺ 448.2.

Examples 108-255

Part A: Preparation of 3-chloro-5,6-dihydro-1H-pyridin-2-one. A solutionof piperidin-2-one (900 g, 9.08 mol) in chloroform (2 L) was added to astirred mixture of phosphorous pentachloride (5.66 kg, 27.2 mol) inchloroform (10 L). Additional chloroform (6 L) was added, and themixture heated under reflux for 21 h. The cooled mixture was added toice while keeping the temperature around 10° C. The pH was adjusted to9-10 by adding 50% aqueous sodium hydroxide while keeping thetemperature below 40° C. The phases were separated and the aqueous phaseextracted with dichloromethane (5 L). The combined organic phases werewashed with brine (5 L), dried, and concentrated under vacuum to give1-benzyl-3,3-dichloro-piperidin-2-one (1200 g, 79%), which was used forthe following step without further purification.

Part B: Preparation of 3-chloro-5,6-dihydro-1H-pyridin-2-one. Lithiumchloride (290 g, 6.84 mol) and lithium carbonate (505 g, 6.84 mol) wereadded to a stirred mixture of 1-benzyl-3,3-dichloro-piperidin-2-one(1150 g, 6.84 mol) in dimethylformamide (4.8 L) and the mixture heatedat 130° C. for 4.5 h. The reaction mixture was cooled to 70° C. and thenconcentrated in vacuo to remove approximately 3 L of dimethylformamide.The mixture was cooled to 45-50° C. and ethyl acetate (4.5 L) was added.The mixture was cooled to 0-5° C. overnight. The resulting mixture wasfiltered through diatomaceous earth, washing the filter bed with ethylacetate (4.5 L). The filtrate was concentrated under vacuum, and theresidue was purified by chromatography (9:1 dichloromethane/methanol)followed by trituration with hexanes/toluene (3:1) to give3-chloro-5,6-dihydro-1H-pyridin-2-one (620 g, 70%).

Part C: Preparation of 1-benzyl-3-chloro-5,6-dihydro-1H-pyridin-2-one. Amixture of 3-chloro-5,6-dihydro-1H-pyridin-2-one (40 g, 304 mmol) andbenzyl bromide (104 g, 608 mmol) in tetrahydrofuran (800 mL) was addedto a suspension of potassium hydride (18.3 g, 456 mmol) intetrahydrofuran (800 mL) at 0° C. After the addition was complete, thereaction mixture was stirred at room temperature for 20 h, then quenchedcautiously with water and extracted with ethyl acetate. The combinedorganic phases were washed with water and brine, dried, and concentratedunder vacuum. The residue was purified by column chromatography (9:1 to1:1 hexanes/ethyl acetate) to give1-benzyl-3-chloro-5,6-dihydro-1H-pyridin-2-one (41 g, 61%).

Part D: Preparation of1-benzyl-3-morpholin-4-yl-5,6-dihydro-1H-pyridin-2-one. A mixture of1-benzyl-3-chloro-5,6-dihydro-1H-pyridin-2-one (41 g, 185 mmol) andmorpholine (500 mL) was heated under reflux for 24 h and thenconcentrated under vacuum. The residue was purified by columnchromatography (7:3 to 1:1 hexanes/ethyl acetate) to give1-benzyl-3-morpholin-4-yl-5,6-dihydro-1H-pyridin-2-one (35.4 g, 70%).

Part E. Preparation of1-benzyl-3-morpholin-4-yl-4-(2,2,2-trifluoro-acetyl)-5,6-dihydro-1H-pyridin-2-one.Trifluoroacetic anhydride (32.8 g, 156 mmol) was added to a solution of1-benzyl-3-morpholin-4-yl-5,6-dihydro-1H-pyridin-2-one (35.4 g, 130mmol) and N,N-dimethyaminopyridine (19.1 g, 156 mmol) in dichloromethane(875 mL) at OC, while maintaining the internal temperature below 5° C.After the addition was complete, the reaction mixture was stirred atroom temperature for 2 h and then quenched with water and extracted withdichloromethane. The combined organic phases were washed with water andthen brine, dried, and concentrated under vacuum to give1-benzyl-3-morpholin-4-yl-4-(2,2,2-trifluoro-acetyl)-5,6-dihydro-1H-pyridin-2-one(44.3 g, 92%), which was used in the following step without furtherpurification.

Part F: Preparation of1-benzyl-4-(2,2,2-trifluoro-acetyl)-piperidine-2,3-dione. A mixture of1-benzyl-3-morpholin-4-yl-4-(2,2,2-trifluoro-acetyl)-5,6-dihydro-1H-pyridin-2-one(44.3 g, 120 mmol), diethyl ether (1300 mL), and 6 M hydrochloric acid(1300 mL) was stirred at room temperature for 16 h and then extractedwith tert-butyl methyl ether. The combined extracts were washed withwater and then with brine, dried, and concentrated under vacuum to give1-benzyl-4-(2,2,2-trifluoro-acetyl)-piperidine-2,3-dione (31.8 g, 89%),which was used in the following step without further purification.

Part G: Preparation of2-(6-benzyl-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl)-5-methoxy-benzoicacid methyl ester. A mixture of1-benzyl-4-(2,2,2-trifluoro-acetyl)-piperidine-2,3-dione (13.2 g, 44.1mmol) and 2-hydrazino-5-methoxy-benzoic acid methyl ester hydrochloride(14.4 g, 61.7 mmol) in acetic acid (400 mL) was heated under reflux for22 h and then concentrated under vacuum. The residue was purified bycolumn chromatography (2:1 hexanes/ethyl acetate) to give2-(6-benzyl-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl)-5-methoxy-benzoicacid methyl ester (15 g, 74%).

Part H: Preparation of5-Methoxy-2-(7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl)-benzoicacid methyl ester. A mixture of2-(6-benzyl-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl)-5-methoxy-benzoicacid methyl ester (22 g, 47.9 mmol), 20% Pd(OH)₂/C (9.8 g), methanol(120 mL), and 4M hydrochloric acid in dioxane (50 mL) was hydrogenatedat 50 psi hydrogen at 50° C. for 90 h. The mixture was cautiouslyfiltered through diatomaceous earth, and the filtrate was concentratedunder vacuum. The residue was purified by column chromatography (7:3hexanes/ethyl acetate) to give5-methoxy-2-(7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl)-benzoicacid methyl ester (11 g, 62%).

Part I: Preparation of5-methoxy-2-(7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl)-benzoicacid bis-potassium salt. Potassium hydroxide pellets (118 mg, 2.1 mmol)were dissolved in methanol (5 mL) with stirring.5-Methoxy-2-(7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl)-benzoicacid methyl ester (370 mg, 1.0 mmol) was added in one portion withstirring. The solid did not completely dissolve before microwave heatingat 120° C. for 15 minutes. The solution was evaporated under a nitrogenstream to give a colorless residue. LC/MS M−H=354.4.

Part J: Preparation of2-[6-(4-dimethylcarbamoyl-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzoicacid. 4-Iodo-N,N-dimethylbenzamide (410 mg, 1.5 mmol) andtetrakisacetonitrilecopper(I) hexafluorophosphate (37.2 mg, 0.1 mmol)were dissolved in degassed dimethylsulfoxide (5 mL) and added to5-methoxy-2-(7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl)-benzoicacid bis-potassium salt. This mixture was vigorously stirred to dissolvethe solids. The solution was purged with nitrogen before heating in amicrowave at 150° C. for 60 minutes. After cooling to ambienttemperature the resulting brown solution was quickly added to aqueous 1Nhydrochloric acid (100 ml) to produce a yellow suspension which wasstirred for 30 minutes. The yellow solid was collected by filtration andwashed with water (30 mL), dissolved in ethyl acetate (50 mL) andextracted into aqueous sodium bicarbonate (20 mL water and 3 mLsaturated sodium bicarbonate). The ethyl acetate was extracted a secondtime with aqueous sodium bicarbonate and the aqueous extracts combinedand washed with ethyl acetate (50 mL). The aqueous extract was acidifiedwith aqueous 1N hydrochloric acid (15 mL) and extracted twice with ethylacetate (30 mL). The combined ethyl acetate extracts were washed withwater (20 mL), dried over sodium sulfate, filtered, and evaporated togive 410 mg (80%) of2-[6-(4-dimethylcarbamoyl-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxybenzoicacid as an amber glass in 85% purity. LC/MS (M+H)⁺: 503.3. ¹H NMR(CD₃OD) δ 7.53 (d, J=2.9 1H), 7.40 (m, 5H), 7.2 (dd, J=2.9, 8.8 Hz, 1H),4.10 (t, J=6.6 Hz, 2H), 3.85 (s, 3H), 3.15 (t, J=6.6 Hz, 2H), 3.05 (s,3H), 2.95 (s, 3H).

Preparation of2-[6-(4-dimethylcarbamoyl-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxybenzamides:2-[6-(4-dimethylcarbamoyl-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxybenzoicacid (10 mg, 0.020 mmol),1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (5.8 mg,0.030 mmol), 1-hydroxybenzotriazole (4.6 mg, 0.030 mmol), andN,N-diisopropylethyl amine (18 mL, 0.100 mmol) were combined indichloromethane (0.350 mL). After 15 minutes, this solution was added toa mixture of the amine and n-methylpyrrolidinone (0.050 mL) and shakenat ambient temperature for 12 h. The solvent was evaporated underreduced pressure and the residue was purified by reverse phase HPLC,collecting products using a MS trigger. TABLE 5 Ex. Structure MF (M +H)⁺ 108

C₂₄H₂₂F₃N₅O₄ 502.2 109

C₃₃H₃₁F₃N₆O₅ 649.2 110

C₃₁H₃₅F₃N₆O₆ 645.3 111

C₃₇H₃₈F₃N₇O₇ 750.3 112

C₃₂H₃₈F₃N₇O₅ 658.3 113

C₃₄H₃₂ClF₃N₆O₅ 697.2 114

C₃₅H₃₅F₃N₆O₆ 693.3 115

C₃₄H₃₁F₃N₆O₇ 693.2 116

C₂₉H₃₁F₃N₆O₅ 601.2 117

C₃₄H₃₁F₃N₆O₇ 693.2 118

C₃₄H₃₁F₃N₆O₇ 693.2 119

C₂₈H₃₀F₃N₅O₅ 574.2 120

C₃₃H₃₂F₃N₅O₄ 620.2 121

C₃₁H₂₆F₃N₅O₆ 622.2 122

C₂₆H₂₆F₃N₅O₄ 530.2 123

C₃₂H₃₀F₃N₅O₅ 622.2 124

C₃₁H₂₇ClF₃N₅O₄ 626.2 125

C₃₁H₂₆F₃N₅O₆ 622.2 126

C₃₁H₂₆F₃N₅O₆ 622.2 127

C₂₄H₂₂F₃N₅O₄ 502.2 128

C₂₁H₁₇F₃N₄O₃ 431.1 129

C₂₂H₁₉F₃N₄O₃ 445.1 130

C₂₃H₂₁F₃N₄O₃ 459.2 131

C₂₄H₂₃F₃N₄O₃ 473.2 132

C₂₅H₂₅F₃N₄O₃ 487.2 133

C₂₂H₁₉F₃N₄O₄ 461.1 134

C₂₀H₁₆F₃N₅O₃ 432.1 135

C₂₇H₂₆F₃N₅O₄ 542.2 136

C₂₉H₃₀F₃N₅O₄ 570.2 137

C₃₁H₃₅F₃N₆O₄ 613.3 138

C₂₉H₂₆F₃N₅O₅ 582.2 139

C₂₉H₂₆F₃N₅O₄S 598.2 140

C₃₂H₂₈F₃N₅O₆ 636.2 141

C₃₀H₃₃F₃N₆O₅ 615.3 142

C₃₀H₂₇F₃N₆O₄ 593.2 143

C₃₁H₂₉F₃N₆O₄ 607.2 144

C₃₀H₂₇F₃N₆O₄ 593.2 145

C₃₀H₂₇F₃N₆O₄ 593.2 146

C₃₆H₃₇F₃N₆O₄ 675.3 147

C₃₀H₂₆F₃N₅O₄ 578.2 148

C₃₁H₂₈F₃N₅O₅ 608.2 149

C₃₁H₂₈F₃N₅O₅ 608.2 150

C₃₀H₂₅ClF₃N₅O₄ 612.2 151

C₃₁H₂₈F₃N₅O₅ 608.2 152

C₃₂H₃₀F₃N₅O₄ 606.2 153

C₃₁H₂₈F₃N₅O₄ 592.2 154

C₃₁H₂₇F₄N₅O₄ 610.2 155

C₃₁H₂₇ClF₃N₅O₄ 626.2 156

C₃₂H₃₀F₃N₅O₅ 622.2 157

C₃₃H₃₂F₃N₅O₅ 636.2 168

C₂₈H₂₉F₃N₆O₅ 587.2 169

C₂₈H₃₁F₃N₆O₄ 573.2 170

C₂₇H₂₈F₃N₅O₅ 560.2 171

C₂₇H₂₈F₃N₅O₄ 544.2 172

C₂₉H₃₂F₃N₅O₅ 588.2 173

C₃₀H₃₀F₃N₇O₄ 610.2 174

C₂₈H₂₈F₃N₅O₄ 556.2 175

C₃₂H₂₈F₃N₅O₅ 620.2 176

C₂₉H₃₃F₃N₆O₄ 587.3 177

C₃₂H₂₉ClF₃N₅O₄ 640.2 178

C₃₁H₂₇ClF₃N₅O₄ 626.2 179

C₃₂H₂₉F₄N₅O₄ 624.2 180

C₃₃H₃₂F₃N₅O₅ 636.2 181

C₃₂H₂₉ClF₃N₅O₄ 640.2 182

C₃₂H₂₇F₆N₅O₅ 676.2 183

C₃₂H₂₇F₆N₅O₅ 676.2 184

C₃₃H₃₂F₃N₅O₄ 620.2 185

C₃₂H₂₇F₆N₅O₅ 676.2 186

C₃₃H₃₂F₃N₅O₄ 620.2 187

C₃₁H₃₃F₃N₆O₄ 611.3 188

C₃₀H₂₈F₃N₅O₅ 596.2 189

C₃₃H₃₂F₃N₅O₄ 620.2 190

C₃₃H₃₀F₃N₅O₄ 618.2 191

C₃₃H₃₂F₃N₅O₅ 636.2 192

C₂₉H₂₅F₃N₆O₄ 579.2 193

C₃₂H₃₀F₃N₅O₄ 606.2 194

C₃₃H₃₂F₃N₅O₄ 620.2 195

C₃₃H₃₂F₃N₅O₅ 636.2 196

C₃₁H₃₄F₃N₅O₄ 598.3 197

C₂₈H₂₇F₃N₆O₄ 569.2 198

C₃₂H₃₆F₃N₅O₄ 612.3 199

C₂₇H₂₆F₃N₅O₄ 542.2 200

C₂₇H₂₆F₃N₅O₄ 542.2 201

C₂₇H₂₆F₃N₅O₄S 574.2 202

C₂₈H₂₆F₃N₅O₄ 554.2 203

C₂₈H₂₈F₃N₅O₄ 556.2 204

C₂₉H₂₉F₃N₆O₅ 599.2 205

C₃₀H₃₂F₃N₅O₄ 584.2 206

C₂₉H₂₈F₃N₅O₄ 568.2 207

C₃₄H₃₃F₃N₆O₄ 647.3 208

C₃₄H₃₂F₄N₆O₄ 665.2 209

C₂₉H₂₉F₃N₆O₄ 599.2 210

C₂₉H₃₁F₃N₆O₄ 585.2 211

C₃₅H₃₅F₃N₆O₄ 661.3 212

C₃₄H₃₈F₃N₇O₅ 682.3 213

C₃₃H₃₈F₃N₇O₅ 670.3 214

C₂₈H₂₈F₃N₅O₅ 572.2 215

C₃₀H₃₂F₃N₅O₅ 600.2 216

C₂₈H₂₈F₃N₅O₄S 588.2 217

C₃₁H₃₂F₃N₅O₆ 628.2 218

C₂₉H₃₀F₃N₅O₄ 570.2 219

C₃₀H₃₂F₃N₅O₄ 584.2 220

C₃₁H₃₄F₃N₅O₄ 598.3 221

C₃₁H₃₄F₃N₅O₄ 598.3 222

C₃₄H₃₉F₃N₆O₅ 669.3 223

C₃₀H₃₁F₃N₆O₅ 613.2 224

C₃₀H₃₂F₃N₅O₄ 584.2 225

C₃₁H₃₄F₃N₅O₄ 598.3 226

C₃₁H₃₄F₃N₅O₄ 598.3 227

C₃₅H₃₄F₃N₅O₄ 646.3 228

C₃₀H₃₂F₃N₅O₄ 584.2 229

C₃₃H₃₂F₃N₇O₄ 648.3 230

C₃₄H₃₃F₃N₆O₄ 647.3 231

C₃₄H₃₉F₃N₆O₄ 653.3 232

C₃₁H₃₅F₃N₆O₄ 613.3 233

C₃₃H₃₀F₃N₅O₄ 618.2 234

C₂₆H₂₆F₃N₅O₄ 530.2 235

C₂₈H₂₆F₃N₅O₄ 554.2 236

C₃₀H₃₅F₃N₆O₄ 601.3 237

C₃₁H₃₇F₃N₆O₄ 615.3 238

C₂₈H₃₀F₃N₅O₄ 558.2 239

C₃₀H₃₄F₃N₅O₄ 586.3 240

C₃₀H₃₂F₃N₅O₅ 600.2 241

C₃₃H₃₇F₃N₆O₄ 639.3 242

C₂₉H₃₂F₃N₅O₄ 572.2 243

C₂₉H₃₂F₃N₅O₄ 572.2 244

C₃₅H₃₅F₃N₆O₄ 661.3 245

C₃₅H₃₅F₃N₆O₄ 661.3 246

C₃₂H₃₇F₃N₆O₄ 627.3 247

C₃₂H₃₁F₃N₆O₄ 621.2 248

C₃₀H₃₄F₃N₅O₆ 618.3 249

C₃₃H₃₇F₃N₆O₄ 639.3 250

C₃₀H₃₁F₃N₆O₅ 613.2 251

C₃₃H₃₁F₃N₆O₆ 665.2 252

C₃₂H₃₆F₃N₅O₄ 612.3 253

C₃₅H₄₁F₃N₆O₄ 667.3 254

C₃₇H₃₉F₃N₆O₄ 689.3 255

C₃₇H₃₉F₃N₆O₄ 689.3

Numerous modifications and variations of the present invention arepossible in light of the above teachings. It is therefore to beunderstood that within the scope of the appended claims, the inventionmay be practiced otherwise that as specifically described herein.

1. A compound of Formula I:P₄-P-M-M₄  I or a stereoisomer or pharmaceutically acceptable salt orsolvate form thereof wherein: M is a 3-10 membered carbocycle or a 4-10membered heterocycle, consisting of: carbon atoms and 1-3 heteroatomsselected from O, S(O)_(p), N, and NZ²; ring M is substituted with 0-3R^(1a) and 0-2 carbonyl groups, and there are 0-3 ring double bonds; Pis fused onto ring M and is a 5, 6, or 7 membered carbocycle or a 5, 6,or 7 membered heterocycle, consisting of: carbon atoms and 1-3heteroatoms selected from O, S(O)_(p), and N; ring P is substituted with0-3 R^(1a) and 0-2 carbonyl groups, and there are 0-3 ring double bonds;alternatively, ring P is absent and P₄ is directly attached to ring M,provided that when ring P is absent, P₄ and M₄ are attached to the 1,2,1,3, or 1,4 positions of ring M; one of P₄ and M₄ is -Z-A-B and theother -G₁-G; G is a group of Formula IIa or IIb:

in formula IIa, ring E is substituted with 1-2 R^(a), provided that atleast one R^(a) is ortho to the point of attachment of ring E; informula IIb, ring D is substituted with 1-2 R^(a), provided that atleast one R^(a) is ortho to the point of attachment of ring D; ring D,including the two atoms of Ring E to which it is attached, is a 5-6membered ring consisting of: carbon atoms and 0-2 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p); ring D is substitutedwith 0-2 R and there are 0-3 ring double bonds; E is selected fromphenyl, pyridyl, pyrimidyl, pyrazinyl, and pyridazinyl, and issubstituted with 0-2 R; alternatively, ring D is absent and ring E isselected from phenyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl,pyrrolyl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, triazolyl,thienyl, and thiazolyl, and ring E is substituted with 0-2 R;alternatively, ring D is absent and ring E is selected from phenyl,pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrazolyl,imidazolyl, isoxazolyl, oxazolyl, triazolyl, thienyl, and thiazolyl, andring E is substituted with 0-1 R and with a 5-6 membered heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p), wherein the 5-6 membered heterocycleis substituted with 0-2 carbonyl and 1-2 R and there are 0-3 ring doublebonds; R is selected from H, C₁₋₄ alkyl, F, Cl, Br, I, OH, OCH₃,OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, CN, C(═NR⁸)NR⁷R⁹, NHC(═NR⁸)NR⁷R⁹,ONHC(═NR⁸)NR⁷R⁹, NR⁸CH(═NR⁷), NH₂, NH(C₁₋₃ alkyl), N(C₁₋₃ alkyl)₂,C(═NH)NH₂, CH₂NH₂, CH₂NH(C₁₋₃ alkyl), CH₂N(C₁₋₃ alkyl)₂, CH₂CH₂NH₂,CH₂CH₂NH(C₁₋₃ alkyl), CH₂CH₂N(C₁₋₃ alkyl)₂, (CR⁸R⁹)_(t)C(O)H,(CR⁸R⁹)_(t)C(O)R^(2c), (CR⁸R⁹)_(t)NR⁷R⁸, (CR⁸R⁹)_(t)C(O)NR⁷R⁸,(CR⁸R⁹)_(t)NR⁷C(O)R⁷, (CR⁸R⁹)_(t)OR³, (CR⁸R⁹)_(t)S(O)_(p)NR⁷R⁸,(CR⁸R⁹)_(t)NR⁷S(O)_(p)R⁷, (CR⁸R⁹)_(t)SR³, (CR⁸R⁹)_(t)S(O)R³,(CR⁸R⁹)_(t)S(O)₂R³, and OCF₃; alternatively, when 2 R groups areattached to adjacent atoms, they combine to form methylenedioxy orethylenedioxy; R^(a) is (CR⁸R⁹)₀₋₃R^(b)(CR⁸R^(2b))₀₋₄R^(b)₀₋₁(CR⁸R⁹)₀₋₄R^(c); R^(b) is selected from O, C(O), C(O)NR³,C(O)N((CH₂)₁₋₃R³), S(O), S(O)₂, S(O)₂NR³, NR³, NR³C(O), NR³S(O)₂,OC(O)NR³, NR³C(O)NR³, and SC(O)NR³; R^(c) is selected from H, OR³,NR³C(O)R³, C(O)R³, CO₂R³, C(O)NR³R^(3a), S(O)₂NR³R^(3a), —CN, C₃₋₁₀carbocycle substituted with 0-2 R⁴, and 5-12 membered heterocyclesubstituted with 0-2 R⁴ and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p);provided that when the (CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₄ portion ofR^(a) is absent, then R^(c) is selected from NR³C(O)R³, S(O)₂NR³R^(3a),C₃₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-12 membered heterocyclesubstituted with 0-2 R⁴ and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p);further provided that when the R^(a) is C(O)—NR*R* and NR*R* is aheterocyclic ring, then the heterocyclic ring is substituted with 1-2R⁴; further provided that the (CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₄R^(c)portion of R^(a) is other than (CR⁸R^(2b))₀₋₃-unsubstituted-phenyl or(CR⁸R⁹)₀₋₃-unsubstituted-phenyl; A is selected from: C₃₋₁₀ carbocyclesubstituted with 0-2 R⁴, and 5-12 membered heterocycle consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p) and substituted with 0-2 R⁴; B is selected from Y,X—Y, N(B¹)C(O)C(R³R^(3g))₁₋₄NB²B³, C(B⁵)═NB⁴, and

provided that Z and B are attached to different atoms on A and that theR^(4d) shown is other than OH; B¹ is selected from H, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃,—(CH₂)₀₋₂—C₃₋₇ carbocycle substituted with 0-2 R^(4b), and —(CH₂)₀₋₂-5-6membered heterocycle consisting of: carbon atoms and 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p) and substitutedwith 0-2 R^(4b); B² is selected from H, C₁₋₆ alkyl substituted with 0-2R^(4c), C(O)R^(2e), C(O)OR^(2d), C(O)NR^(2d)R^(2d),C(O)NH(CH₂)₂NR^(2d)R^(2d), SO₂NR^(2d)R^(2d), C(O)NHSO₂—C₁₋₄ alkyl, andS(O)_(p)R^(5a); B³ is selected from H, C₁₋₆ alkyl substituted with 0-2R^(4c), —(CH₂)₀₋₂-3-6 membered carbocycle substituted with 0-2 R⁵, and a—(CH₂)₀₋₂-4-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-2 R⁵; B⁴ is selected from H, SO₂R^(3b), C(O)R^(3b),SO₂NR³R^(3b), C(O)NR³R^(3b), OR², SR², —CN, and NO₂; B⁵ is NR²R^(2f) orCR³R²R^(2f); Q¹ and Q² are each N; alternatively, Q¹ is CR³ and R^(4d)is NR²R^(2a) or NR^(3a)B⁴, provided that when Q¹ is CR³, then this R³group optionally forms a ring with the R² group of R^(4d), this ring isa 5-6 membered ring consisting of, in addition to the C—C—N shown,carbon atoms and from 0-1 additional heteroatoms selected from N, O, andS(O)_(p), and this ring is substituted with 0-1 R⁵; ring Q is a 5-8membered ring consisting of, in addition to the Q¹-CR^(4d)=Q² groupshown, carbon atoms and 0-2 heteroatoms selected from N, O, andS(O)_(p), and the ring is substituted with an additional 0-2 R^(4d); Yis selected from: CY¹Y²R^(4a), NR³R^(3a), C(O)NR³R^(3a), C₃₋₁₀carbocycle substituted 0-2 R⁴ and 0-1 R^(4a), and, 3-10 memberedheterocycle consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p) and substituted with 0-2R⁴ and 0-1 R^(4a); Y¹ and Y² are independently C₁₋₄ alkyl substitutedwith 0-2 R⁴; X is absent or is selected from —(CR²R^(2a))₁₋₄—,—CR²(CR²R^(2b))(CH₂)_(t)—, —C(O)—, —C(═NR^(1b))—, —CR²(NR^(1b)R²)—,—CR²(OR²)—, —CR²(SR²)—, —C(O)CR²R^(2a)—, —CR²R^(2a)C(O), —S(O)—,—S(O)₂—, —SCR²R^(2a)—, —S(O)CR²R^(2a)—, —S(O)₂CR²R^(2a)—,—CR²R^(2a)S(O)—, —CR²R^(2a)S(O)₂—, —S(O)₂NR²CR²R^(2a)—, —NR²S(O)₂—,—CR²R^(2a)NR²S(O)₂—, —NR²S(O)₂CR²R^(2a)—, —NR²C(O)—, —C(O)NR²CR²R^(2a)—,—NR²C(O)CR²R^(2a)—, —CR²R^(2a)NR²C(O)—, —NR²CR²R^(2a)—, and—OCR²R^(2a)—; G₁ is absent or is selected from (CR³R^(3a))₁₋₅,(CR³R^(3a))₀₋₂CR³═CR³(CR³R^(3a))₀₋₂, (CR³R^(3a))₀₋₂C≡C(CR³R^(3a))₀₋₂,(CR³R^(3a))_(u)C(O)(CR³R^(3a))_(w), (CR³R^(3a))_(u)C(O)O(CR³R^(3a))_(w),(CR³R^(3a))_(u)OC(O)(CR³R^(3a))_(w), (CR³R^(3a))_(u)O(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)C(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)C(O)(CR³R^(3a))_(w),(CR³R^(3a))_(u)OC(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)C(O)O(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)C(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)C(S)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(CR³R^(3a))_(w), (CR³R^(3a))_(u)S(O)(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(O)₂(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)S(O)₂(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(O)₂NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)S(O)₂NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3e)(CR³R^(3a))_(w),(CR³R^(3a))_(u)C(O)(CR³R^(3a))_(u)C(O)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)(CR³R^(3a))_(u)C(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)C(O)(CR³R^(3a))_(u)C(O)(CR³R^(3a))_(w),(CR³R^(3a))_(u)C(O)(CR³R^(3a))_(u)C(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)C(O)(CR³R^(3a))_(u)C(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(O)₂NR^(3b)C(O)(CR³R^(3a))_(w),(CR³R^(3a))_(u)C(O)NR^(3b)S(O)₂(CR³R^(3a))_(w), and(CR³R^(3a))_(u)S(O)₂NR^(3b)C(O)NR^(3b)CR³R^(3a))_(w), wherein u+w total0, 1, 2, 3, or 4 and the right side of G₁ is attached to ring G,provided that G₁ does not form an N—S, NCH₂N, NCH₂O, or NCH₂S bond witheither group to which it is attached; Z is selected from a bond,—(CR³R^(3e))₁₋₄—, (CR³R^(3e))_(q)O(CR³R^(3e))_(q1),(CR³R^(3e))_(q)NR^(3b)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)C(O)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)C(O)O(CR³R^(3e))_(q1),—(CR³R^(3e))_(q)OC(O)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)C(O)NR^(3b)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)NR^(3b)C(O)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)OC(O)O(CR³R^(3e))_(q1),(CR³R^(3e))_(q)OC(O)NR^(3b)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)NR^(3b)C(O)O(CR³R^(3e))_(q1),(CR³R^(3e))_(q)NR^(3b)C(O)NR^(3b)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)C(O)(CR³R^(3e))_(q)C(O)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)NR^(3b)(CR³R^(3e))_(q)C(O)NR^(3b)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)NR^(3b)C(O)(CR³R^(3e))_(q)C(O)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)C(O)(CR³R^(3e))_(q)C(O)NR^(3b)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)NR^(3b)C(O)(CR³R^(3e))_(q)C(O)NR^(3b)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)S(CR³R^(3e))_(q1), (CR³R^(3e))_(q)S(O)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)S(O)₂(CR³R^(3e))_(q1),(CR³R^(3e))_(q)SO₂NR^(3b)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)NR^(3b)SO₂(CR³R^(3e))_(q1),(CR³R^(3e))_(q)S(O)₂NR^(3b)C(O)(CR³R^(3e))_(q1),(CR³R^(3e))_(q)C(O)NR^(3b)S(O)₂(CR³R^(3e))_(q1), and(CR³R^(3e))_(q)NR^(3b)SO₂NR^(3b)(CR³R^(3e))_(q1), wherein q+q1 total 0,1, 2, 3, or 4 and the right side of Z is attached to ring A, providedthat Z does not form a N—S, NCH₂N, NCH₂O, or NCH₂S bond with eithergroup to which it is attached; Z² is selected from H, S(O)₂NHR^(3b),C(O)R^(3b), C(O)NHR^(3b), C(O)OR^(3f), S(O)R^(3f), S(O)₂R^(3f), C₁₋₆alkyl substituted with 0-2 R^(1a), C₂₋₆ alkenyl substituted with 0-2R^(1a), C₂₋₆ alkynyl substituted with 0-2 R^(1a), —(C₀₋₄ alkyl)-C₃₋₁₀carbocycle substituted with 0-3 R^(1a), and —(C₀₋₄ alkyl)-5-10 memberedheterocycle substituted with 0-3 R^(1a) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p); R^(1a), at each occurrence, is selected from H,—(CR³R^(3a))_(r)—R^(1b), —(CR³R^(3a))_(r)—CR³R^(1b)R^(1b),—(CR³R^(3a))_(r)—O—(CR³R^(3a))_(r)—R^(1b),—(CR³R^(3a))_(r)—NR²—(CR³R^(3a))_(r)—R^(1b),—(CR³R^(3a))_(r)—S(O)_(p)—(CR³R^(3a))_(r)—R^(1b),—(CR³R^(3a))_(r)—CO₂—(CR³R^(3a))_(r)—R^(1b),—(CR³R^(3a))_(r)—C(O)NR²—(CR³R^(3a))_(r)—R^(1b),—(CR³R^(3a))_(r)—C(O)—(CR³R^(3a))_(r)—R^(1b), —C₂₋₆ alkenylene-R^(1b),—C₂₋₆ alkynylene-R^(1b), and —(CR³R^(3a))_(r)—C(═NR^(1b))NR³R^(1b),provided that R^(1a) forms other than an N-halo, N—S, O—O, or N—CN bond;alternatively, when two R^(1a) groups are attached to adjacent atoms,together with the atoms to which they are attached they form a 5-7membered ring consisting of: carbon atoms and 0-2 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), this ring beingsubstituted with 0-2 R^(4b) and 0-3 ring double bonds; R^(1b) isselected from H, C₁₋₃ alkyl, F, Cl, Br, I, —CN, —NO₂, —CHO,(CF₂)_(r)CF₃, (CR³R^(3a))_(r)OR², NR²R^(2a), C(O)R^(2b), CO₂R^(2b),OC(O)R², CH(CH₂OR²)₂, (CF₂)_(r)CO₂R^(2a), S(O)_(p)R^(2b),NR²(CH₂)_(r)OR², C(═NR^(2c))NR²R^(2a), NR²C(O)R^(2b), NR²C(O)NR²R^(2a),NR²C(O)₂R^(2a), OC(O)NR²R^(2a), C(O)NR²R^(2a), C(O)NR²(CH₂)_(r)OR²,SO₂NR²R^(2a), NR²SO₂R², C(O)NR²SO₂R², C₃₋₆ carbocycle substituted with0-2 R^(4b), and 5-10 membered heterocycle substituted with 0-2 R^(4b)and consisting of carbon atoms and from 1-4 heteroatoms selected fromthe group consisting of N, O, and S(O)_(p), provided that R^(1b) formsother than an O—O, N-halo, N—S, or N—CN bond and provided thatS(O)_(p)R² forms other than S(O)₂H or S(O)H; R², at each occurrence, isselected from H, CF₃, C₁₋₆ alkyl, —(CH₂)_(r)C₃₋₁₀ carbocycle substitutedwith 0-2 R^(4b), and —(CH₂)_(r)-5-10 membered heterocycle consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p), and substituted with 0-2 R^(4b); R^(2a), at eachoccurrence, is selected from H, CF₃, C₁₋₆ alkyl, —(CH₂)_(r)—C₃₋₁₀carbocycle substituted with 0-2 R^(4b), and —(CH₂)_(r)-5-10 memberedheterocycle consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-2 R^(4b); alternatively, NR²R^(2a) forms a 5 or 6 membered saturated,partially saturated or unsaturated ring substituted with 0-2 R^(4b) andconsisting of: 0-1 additional heteroatoms selected from the groupconsisting of N, O, and S(O)_(p); R^(2b), at each occurrence, isselected from CF₃, C₁₋₄ alkoxy substituted with 0-2 R^(4b), C₁₋₆ alkylsubstituted with 0-2 R^(4b), —(CH₂)_(r)—C₃₋₁₀ carbocycle substitutedwith 0-2 R^(4b), and —(CH₂)_(r)-5-10 membered heterocycle consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p), and substituted with 0-2 R^(4b); R^(2c), at eachoccurrence, is selected from CF₃, OH, C₁₋₄ alkoxy, C₁₋₆ alkyl,—(CH₂)_(r)—C₃₋₁₀ carbocycle substituted with 0-2 R^(4b), and—(CH₂)_(r)-5-10 membered heterocycle containing from 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p), andsubstituted with 0-2 R^(4b); R^(2d), at each occurrence, is selectedfrom H, R^(4c), C₁₋₆ alkyl substituted with 0-2 R^(4c),—(CR³R^(3a))_(r)—C₃₋₁₀ carbocycle substituted with 0-2 R^(4c), and—(CR³R^(3a))_(r)-5-10 membered heterocycle substituted with 0-2 R^(4c)and consisting of: carbon atoms and 1-4 heteroatoms selected from thegroup consisting of N, O, and S(O)_(p), provided that R^(2d) forms otherthan a N-halo, N—C-halo, S(O)_(p)-halo, O-halo, N—S, S—N,S(O)_(p)—S(O)_(p), S—O, O—N, O—S, or O—O moiety; alternatively,NR^(2d)R^(2d) forms a 5-10 membered saturated, partially saturated orunsaturated ring substituted with 0-2 R^(4b) and consisting of: 0-1additional heteroatoms selected from the group consisting of N, O, andS(O)_(p); R^(2e), at each occurrence, is selected from H, R^(4c), C₁₋₆alkyl substituted with 0-2 R^(4c), —(CR³R^(3a))_(r)—C₃₋₁₀ carbocyclesubstituted with 0-2 R^(4c), and —(CR³R^(3a))_(r)-5-10 memberedheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), provided that R^(2e) forms other than a C(O)-halo orC(O)—S(O)_(p) moiety; R^(2f) at each occurrence, is selected from H,CF₃, C₁₋₄ alkoxy substituted with 0-2 R^(4b), C₁₋₆ alkyl substitutedwith 0-2 R^(4b), —(CH₂)_(r)—C₃₋₁₀ carbocycle substituted with 0-2R^(4b), and —(CH₂)_(r)-5-10 membered heterocycle consisting of: carbonatoms and 1-4 heteroatoms selected from the group consisting of N, O,and S(O)_(p) and substituted with 0-2 R^(4b); alternatively, CR²R^(2f)forms a 5-8 membered ring consisting of: carbon atoms and 0-2heteroatoms selected from N, O, and S(O)_(p), and this ring issubstituted with 0-2 R^(4b); alternatively, NR²R^(2f) forms a 5-8membered ring consisting of: carbon atoms and 0-2 additional heteroatomsselected from N, O, and S(O)_(p), and this ring is substituted with 0-2R^(4b); alternatively, when B⁴ is SO₂R^(3b) and B⁵ is NR²R^(2f), R^(3b)and R^(2f) combine to form a 5-8 membered ring consisting of: carbonatoms and 0-2 additional heteroatoms selected from N, O, and S(O)_(p),and this ring is substituted with 0-2 R^(4b); alternatively, when B⁴ isC(O)R^(3b) and B⁵ is NR²R^(2f), R^(3b) and R^(2f) combine to form a 5-8membered ring consisting of: carbon atoms and 0-2 additional heteroatomsselected from N, O, and S(O)_(p), and this ring is substituted with 0-2R^(4b); alternatively, when B⁵ is NR²R^(2f), B⁴ and R^(2f) combine toform a 5-8 membered ring consisting of: carbon atoms and 0-2 additionalheteroatoms selected from N, O, and S(O)_(p), and this ring issubstituted with 0-2 R^(4b) and the R² group of NR²R^(2f), in additionto the groups recited below, is selected from SO₂R^(3b), C(O)R^(3b), and—CN; R³, at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, benzyl, andphenyl; R^(3a), at each occurrence, is selected from H, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃,benzyl, and phenyl; alternatively, R³ and R^(3a), together with thenitrogen atom to which they are attached, combine to form a 5 or 6membered saturated, partially unsaturated, or unsaturated ringconsisting of: carbon atoms, the nitrogen atom to which R³ and R^(3a)are attached, and 0-1 additional heteroatoms selected from the groupconsisting of N, O, and S(O)_(p); R^(3b), at each occurrence, isselected from H, C₁₋₆ alkyl substituted with 0-2 R^(1a), C₂₋₆ alkenylsubstituted with 0-2 R^(1a), C₂₋₆ alkynyl substituted with 0-2 R^(1a),—(C₀₋₄ alkyl)-5-10 membered carbocycle substituted with 0-3 R^(1a), and—(C₀₋₄ alkyl)-5-10 membered heterocycle substituted with 0-3 R^(1a) andconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p); R^(3c), at each occurrence, isselected from CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, benzyl, and phenyl; R^(3d), at eachoccurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C₁₋₄ alkyl-phenyl, andC(═O)R^(3c); R^(3e), at each occurrence, is selected from H, SO₂NHR³,SO₂NR³R³, C(O)R³, C(O)NHR³, C(O)OR^(3f), S(O)R^(3f), S(O)₂R^(3f), C₁₋₆alkyl substituted with 0-2 R^(1a), C₂₋₆ alkenyl substituted with 0-2R^(1a), C₂₋₆ alkynyl substituted with 0-2 R^(1a), —(C₀₋₄ alkyl)-5-10membered carbocycle substituted with 0-3 R^(1a), and —(C₀₋₄ alkyl)-5-10membered heterocycle substituted with 0-3 R^(1a) and consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p); R^(3f) at each occurrence, is selected from: C₁₋₆alkyl substituted with 0-2 R^(1a), C₂₋₆ alkenyl substituted with 0-2R^(1a), C₂₋₆ alkynyl substituted with 0-2 R^(1a), —(C₀₋₄ alkyl)-5-10membered carbocycle substituted with 0-3 R^(1a), and —(C₀₋₄ alkyl)-5-10membered heterocycle substituted with 0-3 R^(1a) and consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p); R^(3g), at each occurrence, is selected from H, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃,C(CH₃)₃, —(CH₂)_(r)-3-6 membered carbocycle, and —(CH₂)_(r)-5-6 memberedheterocycle consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p); alternatively,CR³R^(3g) forms a cyclopropyl group; R⁴, at each occurrence, is selectedfrom ═O, CHO, (CR³R^(3a))_(r)OR², (CR³R^(3a))_(r)F, (CR³R^(3a))_(r)Cl,(CR³R^(3a))_(r)Br, (CR³R^(3a))_(r)I, C₁₋₄ alkyl, (CR³R^(3a))_(r)CN,(CR³R^(3a))_(r)NO₂, (CR³R^(3a))_(r)NR²R^(2a), (CR³R^(3a))_(r)C(O)R^(2c),(CR³R^(3a))_(r)NR²C(O)R^(2b), (CR³R^(3a))_(r)C(O)NR²R^(2a),(CR³R^(3a))_(r)NR²C(O)NR²R^(2a), (CR³R^(3a))_(r)C(═NR²)NR²R^(2a),(CR³R^(3a))_(r)C(═NS(O)₂R⁵)NR²R^(2a),(CR³R^(3a))_(r)NR²C(═NR²)NR²R^(2a),(CR³R^(3a))_(r)C(O)NR²C(═NR²)NR²R^(2a), (CR³R^(3a))_(r)SO₂NR²R^(2a),(CR³R^(3a))_(r)NR²SO₂NR²R^(2a), (CR³R^(3a))_(r)NR²SO₂—C₁₋₄ alkyl,(CR³R^(3a))_(r)NR²SO₂R⁵, (CR³R^(3a))_(r)S(O)_(p)R^(5a),(CR³R^(3a))_(r)(CF₂)_(r)CF₃, NHCH₂R^(1b), OCH₂R^(1b), SCH₂R^(1b),NH(CH₂)₂(CH₂)_(t)R^(1b), O(CH₂)₂(CH₂)_(t)R^(1b), S(CH₂)₂(CH₂)_(t)R^(1b),(CR³R^(3a))_(r)-5-6 membered carbocycle substituted with 0-1 R⁵, and a(CR³R^(3a))_(r)-5-6 membered heterocycle consisting of: carbon atoms and1-4 heteroatoms selected from the group consisting of N, O, and S(O)_(p)and substituted with 0-1 R⁵; R^(4a) is selected from C₁₋₆ alkylsubstituted with 0-2 R^(4c), C₂₋₆ alkenyl substituted with 0-2 R^(4c),C₂₋₆ alkynyl substituted with 0-2 R^(4c), —(CR³R^(3g))_(r)—C₅₋₁₀membered carbocycle substituted with 0-3 R^(4c), —(CR³R^(3g))_(r)-5-10membered heterocycle substituted with 0-3 R^(4c) and consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p), (CR³R^(3g))_(r)CN,(CR³R^(3g))_(r)C(═NR^(2d))NR^(2d)R^(2d),(CR³R^(3g))_(r)NR^(2d)C(═NR^(2d))NR^(2d)R^(2d),(CR³R^(3g))_(r)NR^(2d)C(R^(2e))(═NR^(2d)), (CR³R^(3g))_(r)NR^(2d)R^(2d),(CR³R^(3g))_(r)N(→O)R^(2d)R^(2d), (CR³R^(3g))_(r)OR^(2d),(CR³R^(3g))_(r)—NR^(2d)C(O)R^(2e), (CR³R^(3g))_(r)—C(O)R^(2e),(CR³R^(3g))_(r)—OC(O)R^(2e), (CR³R^(3g))_(r)—C(O)NR^(2d)R^(2d),(CR³R^(3g))_(r)—C(O)OR^(2d), (CR³R^(3g))_(r)—NR^(2d)C(O)NR^(2d)R^(2d),(CR³R^(3g))_(r)—OC(O)NR^(2d)R^(2d), (CR³R^(3g))_(r)—NR^(2d)C(O)OR^(2d),(CR³R^(3g))_(r)—SO₂NR^(2d)R^(2d),(CR³R^(3g))_(r)—NR^(2d)SO₂NR^(2d)R^(2d),(CR³R^(3g))_(r)—C(O)NR^(2d)SO₂R^(2d), (CR³R^(3g))_(r)—NR^(2d)SO₂R^(2d),and (CR³R^(3g))_(r)—S(O)_(p)R^(2d), provided that S(O)_(p)R^(2d) formsother than S(O)₂H or S(O)H and further provided that R^(4a) is otherthan a hydroxamic acid; R^(4b), at each occurrence, is selected from H,═O, (CH₂)_(r)OR³, (CH₂)_(r)F, (CH₂)_(r)Cl, (CH₂)_(r)Br, (CH₂)_(r)I, C₁₋₄alkyl, (CH₂)_(r)CN, (CH₂)_(r)NO₂, (CH₂)_(r)NR³R^(3a), (CH₂)_(r)C(O)R³,(CH₂)_(r)C(O)OR^(3c), (CH₂)_(r)NR³C(O)R^(3a), (CH₂)_(r)—C(O)NR³R^(3a),(CH₂)_(r)NR³C(O)NR³R^(3a), (CH₂)_(r)—C(═NR³)NR³R^(3a),(CH₂)_(r)NR³C(═NR³)NR³R^(3a), (CH₂)_(r)SO₂NR³R^(3a),(CH₂)_(r)NR³SO₂NR³R^(3a), (CH₂)_(r)NR³SO₂—C₁₋₄ alkyl,(CH₂)_(r)NR³SO₂CF₃, (CH₂)_(r)NR³SO₂-phenyl, (CH₂)_(r)S(O)_(p)CF₃,(CH₂)_(r)S(O)_(p)—C₁₋₄ alkyl, (CH₂)_(r)S(O)_(p)-phenyl, and(CH₂)_(r)(CF₂)_(r)CF₃; R^(4c), at each occurrence, is selected from ═O,(CR³R^(3a))_(r)OR², (CR³R^(3a))_(r)F, (CR³R^(3a))_(r)Br,(CR³R^(3a))_(r)Cl, (CR³R^(3a))_(r)CF₃, C₁₋₄ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, (CR³R^(3a))_(r)CN, (CR³R^(3a))_(r)NO₂,(CR³R^(3a))_(r)NR²R^(2a), (CR³R^(3a))_(r)N(→O)R²R^(2a),(CR³R^(3a))_(r)C(O)R^(2c), (CR³R^(3a))_(r)NR²C(O)R^(2b),(CR³R^(3a))_(r)C(O)NR²R^(2a), (CR³R^(3a))_(r)N═CHOR³,(CR³R^(3a))_(r)C(O)NR²(CH₂)₂NR²R^(2a), (CR³R^(3a))_(r)NR²C(O)NR²R^(2a),(CR³R^(3a))_(r)C(═NR²)NR²R^(2a), (CR³R^(3a))_(r)NR²C(═NR²)NR²R^(2a),(CR³R^(3a))_(r)SO₂NR²R^(2a), (CR³R^(3a))_(r)NR²SO₂NR²R^(2a),(CR³R^(3a))_(r)C(O)NR²SO₂—C₁₋₄ alkyl, (CR³R^(3a))_(r)NR²SO₂R^(5a),(CR³R^(3a))_(r)C(O)NR²SO₂R^(5a), (CR³R^(3a))_(r)S(O)_(p)R^(5a),(CF₂)_(r)CF₃, (CR³R^(3a))_(r)C₃₋₁₀ carbocycle substituted with 0-2R^(4b), and (CR³R^(3a))_(r)4-10 membered heterocycle substituted with0-2 R^(4b) and consisting of carbon atoms and from 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p); R^(4d), ateach occurrence, is selected from H, (CR³R^(3a))_(r)OR²,(CR³R^(3a))_(r)F, (CR³R^(3a))_(r)Br, (CR³R^(3a))_(r)Cl, C₁₋₄ alkyl,(CR³R^(3a))_(r)CN, (CR³R^(3a))_(r)NO₂, (CR³R^(3a))_(r)NR²R^(2a),(CR³R^(3a))_(r)C(O)R^(2c), (CR³R^(3a))_(r)NR²C(O)R^(2b),(CR³R^(3a))_(r)C(O)NR²R^(2a), (CR³R^(3a))_(r)N═CHOR³,(CR³R^(3a))_(r)C(O)NH(CH₂)₂NR²R^(2a), (CR³R^(3a))_(r)NR²C(O)NR²R^(2a),(CR³R^(3a))_(r)C(═NR²)NR²R^(2a), (CR³R^(3a))_(r)NHC(═NR²)NR²R^(2a),(CR³R^(3a))_(r)SO₂NR²R^(2a), (CR³R^(3a))_(r)NR²SO₂NR²R^(2a),(CR³R^(3a))_(r)NR²SO₂—C₁₋₄ alkyl, (CR³R^(3a))_(r)C(O)NHSO₂—C₁₋₄ alkyl,(CR³R^(3a))NR²SO₂R⁵, (CR³R^(3a))_(r)S(O)_(p)R^(5a),(CR³R^(3a))_(r)(CF₂)_(r)CF₃, (CR³R^(3a))_(r)-5-6 membered carbocyclesubstituted with 0-1 R⁵, and a (CR³R^(3a))_(r)-5-6 membered heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p) and substituted with 0-1 R⁵; R⁵, ateach occurrence, is selected from H, C₁₋₆ alkyl, ═O, (CH₂)_(r)OR³, F,Cl, Br, I, —CN, NO₂, (CH₂)_(r)NR³R^(3a), (CH₂)_(r)C(O)R³,(CH₂)_(r)C(O)OR^(3c), (CH₂)_(r)NR³C(O)R^(3a), (CH₂)_(r)C(O)NR³R^(3a),(CH₂)_(r)NR³C(O)NR³R^(3a), (CH₂)_(r)CH(═NOR^(3d)),(CH₂)_(r)C(═NR³)NR³R^(3a), (CH₂)_(r)NR³C(═NR³)NR³R^(3a),(CH₂)_(r)SO₂NR³R^(3a), (CH₂)_(r)NR³SO₂NR³R^(3a), (CH₂)_(r)NR³SO₂—C₁₋₄alkyl, (CH₂)_(r)NR³SO₂CF₃, (CH₂)_(r)NR³SO₂-phenyl, (CH₂)_(r)S(O)_(p)CF₃,(CH₂)_(r)S(O)_(p)—C₁₋₄ alkyl, (CH₂)_(r)S(O)_(p)-phenyl, (CF₂)_(r)CF₃,phenyl substituted with 0-2 R⁶, naphthyl substituted with 0-2 R⁶, andbenzyl substituted with 0-2 R⁶; R^(5a), at each occurrence, is selectedfrom C₁₋₆ alkyl, (CH₂)_(r)OR³, (CH₂)_(r)NR³R^(3a), (CH₂)_(r)C(O)R³,(CH₂)_(r)C(O)OR^(3c), (CH₂)_(r)NR³C(O)R^(3a), (CH₂)_(r)C(O)NR³R^(3a),(CF₂)_(r)CF₃, phenyl substituted with 0-2 R⁶, naphthyl substituted with0-2 R⁶, and benzyl substituted with 0-2 R⁶, provided that R^(5a) doesnot form a S—N or S(O)_(p)—C(O) bond; R⁶, at each occurrence, isselected from H, OH, (CH₂)_(r)OR², halo, C₁₋₄ alkyl, CN, NO₂,(CH₂)_(r)NR²R^(2a), (CH₂)_(r)C(O)R^(2b), NR²C(O)R^(2b),NR²C(O)NR²R^(2a), C(═NH)NH₂, NHC(═NH)NH₂, SO₂NR²R^(2a), NR²SO₂NR²R^(2a),and NR²SO₂C₁₋₄ alkyl; R⁷, at each occurrence, is selected from H, OH,C₁₋₆ alkyl, C₁₋₆ alkyl-C(O)—, C₁₋₆ alkyl-O—, (CH₂)_(n)-phenyl, C₁₋₄alkyl-OC(O)—, C₆₋₁₀ aryl-O—, C₆₋₁₀ aryl-OC(O)—, C₆₋₁₀ aryl-CH₂—C(O)—,C₁₋₄ alkyl-C(O)O—C₁₋₄ alkyl-OC(O)—, C₆₋₁₀ aryl-C(O)O—C₁₋₄ alkyl-OC(O)—,C₁₋₆ alkyl-NH₂—C(O)—, phenyl-NH₂—C(O)—, and phenyl-C₁₋₄ alkyl-C(O)—; R⁸,at each occurrence, is selected from H, C₁₋₆ alkyl, and(CH₂)_(n)-phenyl; alternatively, R⁷ and R⁸, when attached to the samenitrogen, combine to form a 5-10 membered heterocyclic ring consistingof carbon atoms and 0-2 additional heteroatoms selected from the groupconsisting of N, O, and S(O)_(p); R⁹, at each occurrence, is selectedfrom H, C₁₋₆ alkyl, and (CH₂)_(n)-phenyl; n, at each occurrence, isselected from 0, 1, 2, and 3; p, at each occurrence, is selected from 0,1, and 2; r, at each occurrence, is selected from 0, 1, 2, 3, 4, 5, and6; and t, at each occurrence, is selected from 0, 1, 2, and
 3. 2. Acompound according to claim 1, wherein the compound is of Formula II:

or a stereoisomer or pharmaceutically acceptable salt or solvate formthereof, wherein: ring M, including P₁, P₂, M₁, and M₂, is a 5, 6, or 7membered carbocycle or a 5, 6, or 7 membered heterocycle, consisting of:carbon atoms and 1-3 heteroatoms selected from O, S(O)_(p), N, and NZ²;ring M is substituted with 0-2 R^(1a) and 0-2 carbonyl groups, and thereare 0-3 ring double bonds; ring P, including P₁, P₂, and P₃, is a 5 or 6membered aromatic heterocycle, consisting of: carbon atoms and 1-3heteroatoms selected from O, S(O)_(p), and N; alternatively, ring P,including P₁, P₂, and P₃, is a 5 or 6 membered dihydro-aromaticheterocycle, consisting of: carbon atoms and 1-3 heteroatoms selectedfrom O, S(O)_(p), and N; ring P is substituted with 0-2 R^(1a); one ofP₄ and M₄ is -Z-A-B and the other -G₁-G; G is a group of Formula IIa orIIb:

in formula IIa, ring E is substituted with 1-2 R^(a), provided that atleast one R^(a) is ortho to the point of attachment of ring E; informula IIb, ring D is substituted with 1-2 R^(a), provided that atleast one R^(a) is ortho to the point of attachment of ring D; ring D,including the two atoms of Ring E to which it is attached, is a 5-6membered ring consisting of: carbon atoms and 0-2 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p); ring D is substitutedwith 0-2 R and there are 0-3 ring double bonds; E is selected fromphenyl, pyridyl, pyrimidyl, pyrazinyl, and pyridazinyl, and issubstituted with 0-2 R; alternatively, ring D is absent, and ring E isselected from phenyl, pyridyl, pyrimidyl, and thienyl, and ring E issubstituted with 0-2 R; alternatively, ring D is absent, ring E isselected from phenyl, pyridyl, and thienyl, and ring E is substitutedwith 0-2 R and a 5-6 membered heterocycle consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), wherein the 5-6 membered heterocycle is substituted with 0-2carbonyl and 1-2 R and there are 0-3 ring double bonds; R is selectedfrom H, C₁₋₄ alkyl, F, Cl, OH, OCH₃, OCH₂CH₃, OCH(CH₃)₂, CN, C(═NH)NH₂,C(═NH)NHOH, C(═NH)NHOCH₃, NH₂, NH(C₁₋₃ alkyl), N(C₁₋₃ alkyl)₂,C(═NH)NH₂, CH₂NH₂, CH₂NH(C₁₋₃ alkyl), CH₂N(C₁₋₃ alkyl)₂,(CR⁸R⁹)_(t)NR⁷R⁸, C(O)NR⁷R⁸, CH₂C(O)NR⁷R⁸, S(O)_(p)NR⁷R⁸,CH₂S(O)_(p)NR⁷R⁸, SO₂R³, and OCF₃; alternatively, when 2 R groups areattached to adjacent atoms, they combine to form methylenedioxy orethylenedioxy; R^(a) is (CR⁸R⁹)₀₋₁R^(b)(CR⁸R^(2b))₀₋₄R^(b)₀₋₁(CR⁸R⁹)₀₋₁R^(c); R^(b) is selected from O, C(O), C(O)NR³,C(O)N((CH₂)₂₋₃R³), S(O), S(O)₂, S(O)₂NR³, NR³, NR³C(O), and NR³S(O)₂;R^(c) is selected from H, OR³, NR³C(O)R³, C(O)R³, CO₂R³, C(O)NR³R^(3a),S(O)₂NR³R^(3a), —CN, C₃₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-12membered heterocycle substituted with 0-2 R⁴ and consisting of: carbonatoms and 1-4 heteroatoms selected from the group consisting of N, O,and S(O)_(p); R^(c) is selected from H, OR³, NR³C(O)R³, C(O)R³, CO₂R³,C(O)NR³R^(3a), S(O)₂NR³R^(3a), C₅₋₁₀ carbocycle substituted with 0-2 R⁴,and 5-10 membered heterocycle substituted with 0-2 R⁴ and consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p); provided that when the (CR⁸R^(2b))₀₋₄R^(b)₀₋₁(CR⁸R⁹)₀₋₁ portion of R^(a) is absent, then R^(c) is selected fromNR³C(O)R³, S(O)₂NR³R^(3a), C₅₋₁₀ carbocycle substituted with 0-2 R⁴, and5-10 membered heterocycle substituted with 0-2 R⁴ and consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p); further provided that when the R^(a) is C(O)—NR*R*and NR*R* is a heterocyclic ring, then the heterocyclic ring issubstituted with 1-2 R⁴; further provided that the (CR⁸R^(2b))₀₋₄R^(b)₀₋₁(CR⁸R⁹)₀₋₄R^(c) portion of R^(a) is other than(CR⁸R^(2b))₀₋₃-unsubstituted-phenyl or (CR⁸R⁹)₀₋₃-unsubstituted-phenyl;A is selected from: C₅₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-10membered heterocycle consisting of: carbon atoms and 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p) and substitutedwith 0-2 R⁴; B is selected from Y, X—Y, N(B¹)C(O)C(R³R^(3g))NB²B³,N(B¹)C(O)C(R³R^(3g))C(R³R^(3g))NB²B³,

provided that Z and B are attached to different atoms on A, the R^(4d)shown is other than OH, and that the A-X—N moiety forms other than aN—N—N group; B¹ is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, —(CH₂)₀₋₁—C₃₋₇carbocycle substituted with 0-2 R^(4b), and —(CH₂)₀₋₁-5-6 memberedheterocycle consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p) and substituted with 0-2R^(4b); B² is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, NR^(2d)R^(2d),CH₂—NR^(2d)R^(2d), CH₂CH₂—NR^(2d)R^(2d), C(O)R^(2e), C(O)NR^(2d)R^(2d),SO₂NR^(2d)R^(2d), and S(O)_(p)R^(5a); B³ is selected from H, C₁₋₆ alkylsubstituted with 0-1 R^(4c), —(CH₂)₀₋₁-3-6 membered carbocyclesubstituted with 0-1 R⁵, and a —(CH₂)₀₋₁-5-6 membered heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p) and substituted with 0-1 R⁵; B⁴ isselected from H, SO₂R^(3b), C(O)R^(3b), SO₂NR³R^(3b), C(O)NR³R^(3b),OR², and —CN; B⁵ is NR²R^(2f) or CR³R²R^(2f); ring Q is a 5-6 memberedring consisting of, in addition to the Q¹-CR^(4d)=Q² group shown, carbonatoms and 0-2 heteroatoms selected from N, O, and S(O)_(p), and the ringis substituted with an additional 0-2 R^(4d); Q¹ and Q² are each N;alternatively, Q¹ is CR³ and R^(4d) is NR²R^(2a) or NR^(3a)B⁴, providedthat when Q¹ is CR³, then this R³ group optionally forms a ring with theR² group of R^(4d), this ring is a 5-6 membered ring consisting of, inaddition to the C—C—N shown, carbon atoms and from 0-1 additionalheteroatoms selected from N, O, and S(O)_(p), and this ring issubstituted with 0-1 R⁵; Q⁴ is selected from C═O and SO₂; ring Q³ is a4-7 membered monocyclic or tricyclic ring consisting of, in addition tothe N-Q⁴ group shown, carbon atoms and 0-2 heteroatoms selected fromNR^(4c), O, S, S(O), and S(O)₂, wherein: 0-2 double bonds are presentwithin the ring and the ring is substituted with 0-2 R⁴; alternatively,ring Q³ is a 4-7 membered ring to which another ring is fused, wherein:the 4-7 membered ring consists of, in addition to the shown amide group,carbon atoms and 0-2 heteroatoms selected from NR^(4c), O, S, S(O), andS(O)₂ and 0-1 double bonds are present within the ring; the fusion ringis phenyl or a 5-6 membered heteroaromatic consisting of carbon atomsand 1-2 heteroatoms selected from NR^(4c), O, and S; ring Q³, whichincludes the 4-7 membered ring and the fusion ring, is substituted with0-3 R⁴; ring Q⁵ is a C₃₋₇ monocyclic carbocycle or 3-7 memberedmonocyclic heterocycle, wherein the carbocycle or heterocycle consistsof: carbon atoms and 0-2 heteroatoms selected from N, O, and S(O)_(p),the carbocycle or heterocycle further comprises 0-2 double bonds and 0-2carbonyl groups, and the carbocycle or heterocycle is substituted with0-2 R⁴; X is selected from —(CR²R^(2a))₁₋₄—, —C(O)—, —C(═NR^(1c))—,—CR²(NR^(1b)R²)—, —C(O)CR²R^(2a)—, —CR²R^(2a)C(O), —C(O)NR²—, —NR²C(O)—,—C(O)NR²CR²R^(2a)—, —NR²C(O)CR²R^(2a)—, —CR²R^(2a)C(O)NR²—,—CR²R^(2a)NR²C(O)—, —NR²C(O)NR²—, —NR²—, —NR²CR²R^(2a)—, —CR²R^(2a)NR²—,—S(O)₂—, —NR²S(O)₂—, O, —CR²R^(2a)O—, and —OCR²R^(2a)—; Y is selectedfrom: CY¹Y²R^(4a), NR³R^(a), and C(O)NR³R^(3a); Y¹ and Y² areindependently C₁₋₃ alkyl substituted with 0-2 R⁴; alternatively, Y isselected from one of the following carbocyclic and heterocycles that aresubstituted with 1 R^(4a) and 0-2 R⁴: cyclopropyl, cyclopentyl,cyclohexyl, phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl,furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl,isoxazolyl, isoxazolinyl, thiazolyl, isothiazolyl, pyrazolyl,imidazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl,1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl,1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl,1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, benzofuranyl,benzothiofuranyl, indolyl, benzimidazolyl, benzoxazolyl, benzthiazolyl,indazolyl, benzisoxazolyl, benzisothiazolyl, and isoindazolyl; Z isselected from a bond, CH₂, CH₂CH₂, CH₂O, OCH₂, C(O), NH, CH₂NH, NHCH₂,CH₂C(O), C(O)CH₂, C(O)NH, NHC(O), NHC(O)CH₂C(O)NH, S(O)₂, CH₂S(O)₂,S(O)₂(CH₂), SO₂NH, and NHSO₂, wherein the right side of Z is attached toring A, provided that Z does not form a N—S, NCH₂N, NCH₂O, or NCH₂S bondwith either group to which it is attached; Z² is selected from H, C₁₋₄alkyl, phenyl, benzyl, C(O)R^(3b), S(O)R^(3f), and S(O)₂R^(3f); R^(1a),at each occurrence, is selected from H, —(CH₂)_(r)—R^(1b),—(CH(CH₃))_(r)—R^(1b), —(C(CH₃)₂)_(r)—R^(1b), —O—(CR³R^(3a))_(r)—R^(1b),—NR²—(CR³R^(3a))_(r)—R^(1b), and —S—(CR³R^(3a))_(r)—R^(1b), providedthat R^(1a) forms other than an N-halo, N—S, O—O, or N—CN bond;alternatively, when two R^(1a) groups are attached to adjacent atoms,together with the atoms to which they are attached they form a 5-7membered ring consisting of: carbon atoms and 0-2 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), this ring beingsubstituted with 0-2 R^(4b) and 0-3 ring double bonds; R^(1b) isselected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, F, Cl, Br, I, —CN,—CHO, CF₃, OR², NR²R^(2a), C(O)R^(2b), CO₂R^(2b), OC(O)R², CO₂R^(2a),S(O)_(p)R², NR²(CH₂)_(r)OR², NR²C(O)R^(2b), NR²C(O)NHR², NR²C(O)₂R^(2a),OC(O)NR²R^(2a), C(O)NR²R^(2a), C(O)NR²(CH₂)_(r)OR², SO₂NR²R^(2a),NR²SO₂R², C₅₋₆ carbocycle substituted with 0-2 R^(4b), and 5-6 memberedheterocycle consisting of carbon atoms and from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-2 R^(4b), provided that R^(1b) forms other than an O—O, N-halo, N—S,or N—CN bond; R², at each occurrence, is selected from H, CF₃, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃,C(CH₃)₃, benzyl substituted with 0-2 R^(4b), C₅₋₆ carbocycle substitutedwith 0-2 R^(4b), a C₅₋₆ carbocyclic-CH₂-group substituted with 0-2R^(4b), and 5-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),and substituted with 0-2 R^(4b); R^(2a), at each occurrence, is selectedfrom H, CF₃, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, benzyl substituted with 0-2 R^(4b),C₅₋₆ carbocycle substituted with 0-2 R^(4b), and 5-6 memberedheterocycle consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-2 R^(4b); alternatively, NR²R^(2a) forms a 5 or 6 membered saturated,partially saturated or unsaturated ring substituted with 0-2 R^(4b) andconsisting of: 0-1 additional heteroatoms selected from the groupconsisting of N, O, and S(O)_(p); R^(2b), at each occurrence, isselected from CF₃, C₁₋₄ alkoxy, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, benzyl substitutedwith 0-2 R^(4b), C₅₋₆ carbocycle substituted with 0-2 R^(4b), and 5-6membered heterocycle consisting of: carbon atoms and 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p), andsubstituted with 0-2 R^(4b); R^(2c), at each occurrence, is selectedfrom CF₃, OH, C₁₋₄ alkoxy, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, benzyl substitutedwith 0-2 R^(4b), C₅₋₆ carbocycle substituted with 0-2 R^(4b), and 5-6membered heterocycle containing from 1-4 heteroatoms selected from thegroup consisting of N, O, and S(O)_(p), and substituted with 0-2 R^(4b);R^(2d), at each occurrence, is selected from H, R^(4c), C₁₋₄ alkylsubstituted with 0-2 R^(4c), —(CR³R^(3a))_(r)—C₃₋₆ carbocyclesubstituted with 0-2 R^(4c), and —(CR³R^(3a))_(r)-5-6 memberedheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), provided that R^(2d) forms other than a N-halo, N—C-halo,S(O)_(p)-halo, O-halo, N—S, S—N, S(O)_(p)—S(O)_(p), S—O, O—N, O—S, orO—O moiety; alternatively, NR^(2d)R^(2d) forms a 5 or 6 memberedsaturated, partially saturated or unsaturated ring substituted with 0-2R^(4b) and consisting of: 0-1 additional heteroatoms selected from thegroup consisting of N, O, and S(O)_(p); R^(2e), at each occurrence, isselected from H, R^(4c), C₁₋₄ alkyl substituted with 0-2 R^(4c),—(CR³R^(3a))_(r)—C₃₋₆ carbocycle substituted with 0-2 R^(4c), and—(CR³R^(3a))_(r)-5-6 membered heterocycle substituted with 0-2 R^(4c)and consisting of: carbon atoms and 1-4 heteroatoms selected from thegroup consisting of N, O, and S(O)_(p), provided that R^(2e) forms otherthan a C(O)-halo or C(O)—S(O)_(p) moiety; R^(2f), at each occurrence, isselected from H, CF₃, C₁₋₄ alkoxy, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, benzyl substitutedwith 0-1 R^(4b), C₅₋₆ carbocycle substituted with 0-2 R^(4b), and 5-6membered heterocycle containing from 1-4 heteroatoms selected from thegroup consisting of N, O, and S(O)_(p) and substituted with 0-2 R^(4b);alternatively, CR²R^(2f) forms a 5-6 membered ring consisting of: carbonatoms and 0-2 heteroatoms selected from N, O, and S(O)_(p), and thisring is substituted with 0-2 R^(4b); alternatively, NR²R^(2f) forms a5-6 membered ring consisting of: carbon atoms and 0-2 additionalheteroatoms selected from N, O, and S(O)_(p), and this ring issubstituted with 0-2 R^(4b); alternatively, when B⁵ is NR²R^(2f), B⁴ andR^(2f) combine to form a 5-6 membered ring consisting of: carbon atomsand 0-2 additional heteroatoms selected from N, O, and S(O)_(p), andthis ring is substituted with 0-2 R^(4b) and the R² group of NR²R^(2f),in addition to the groups recited below, is selected from SO₂R^(3b) andC(O)R^(3b); R³, at each occurrence, is selected from H, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, benzyl, and phenyl; R^(3a), at each occurrence, isselected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzyl, and phenyl;alternatively, R³ and R^(3a), together with the nitrogen atom to whichthey are attached, combine to form a 5 or 6 membered saturated,partially unsaturated, or unsaturated ring consisting of: carbon atomsand the nitrogen atom to which R³ and R^(3a) are attached; R^(3b), ateach occurrence, is selected from H, CF₃, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, —(C₀₋₁ alkyl)-5-6 membered carbocycle substituted with 0-1R^(1a), and —(C₀₋₁ alkyl)-5-6 membered heterocycle substituted with 0-1R^(1a) and consisting of: carbon atoms and 1-4 heteroatoms selected fromthe group consisting of N, O, and S(O)_(p); R^(3c), at each occurrence,is selected from CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzyl, and phenyl;R^(3d), at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂-phenyl, CH₂CH₂-phenyl, and C(═O)R^(3c); R⁴, at eachoccurrence, is selected from ═O, OR², CH₂OR², (CH₂)₂OR², F, Cl, Br, I,C₁₋₄ alkyl, —CN, NO₂, NR²R^(2a), CH₂NR²R^(2a), (CH₂)₂NR²R^(2a),C(O)R^(2c), NR²C(O)R^(2b), C(O)NR²R^(2a), NR²C(O)NR²R^(2a),SO₂NR²R^(2a), NR²SO₂NR²R^(2a), S(O)_(p)R^(5a), NR²SO₂—C₁₋₄ alkyl,NR²SO₂R⁵, CF₃, CF₂CF₃, 5-6 membered carbocycle substituted with 0-1 R⁵,and a 5-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),and substituted with 0-1 R⁵; R^(4b), at each occurrence, is selectedfrom H, ═O, OR³, CH₂OR³, F, Cl, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, —CN, NO₂, NR³R^(3a),CH₂NR³R^(3a), C(O)R³, CH₂—C(O)R³, C(O)OR^(3c), CH₂C(O)OR^(3c),NR³C(O)R^(3a), CH₂NR³C(O)R^(3a), C(O)NR³R^(3a), CH₂C(O)NR³R^(3a),NR³C(O)NR³R^(3a), CH₂NR³C(O)NR³R^(3a), C(═NR³)NR³R^(3a),CH₂C(═NR³)NR³R^(3a), NR³C(═NR³)NR³R^(3a), CH₂NR³C(═NR³)NR³R^(3a),SO₂NR³R^(3a), CH₂SO₂NR³R^(3a), NR³SO₂NR³R^(3a), CH₂NR³SO₂NR³R^(3a),NR³SO₂—C₁₋₄ alkyl, CH₂NR³SO₂—C₁₋₄ alkyl, NR³SO₂CF₃, CH₂NR³SO₂CF₃,NR³SO₂-phenyl, CH₂NR³SO₂-phenyl, S(O)_(p)CF₃, CH₂S(O)_(p)CF₃,S(O)_(p)—C₁₋₄ alkyl, CH₂S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl,CH₂S(O)_(p)-phenyl, CF₃, and CH₂—CF₃; R^(4c), at each occurrence, isselected from ═O, (CR³R^(3a))_(r)OR², (CR³R^(3a))_(r)F,(CR³R^(3a))_(r)Br, (CR³R^(3a))_(r)Cl, (CR³R^(3a))_(r)CF₃, C₁₋₄ alkyl,C₂₋₃ alkenyl, C₂₋₃ alkynyl, (CR³R^(3a))_(r)CN, (CR³R^(3a))_(r)NO₂,(CR³R^(3a))_(r)NR²R^(2a), (CR³R^(3a))_(r)N(→O)R²R^(2a),(CR³R^(3a))_(r)C(O)R^(2c), (CR³R^(3a))_(r)NR²C(O)R^(2b),(CR³R^(3a))_(r)C(O)NR²R^(2a), (CR³R^(3a))_(r)NR²C(O)NR²R^(2a),(CR³R^(3a))_(r)SO₂NR²R^(2a), (CR³R^(3a))_(r)NR²SO₂NR²R^(2a),(CR³R^(3a))_(r)NR²SO₂R^(5a), (CR³R^(3a))_(r)C(O)NR²SO₂R^(5a),(CR³R^(3a))_(r)S(O)_(p)R^(5a), (CF₂)_(r)CF₃, (CR³R^(3a))_(r)C₃₋₁₀carbocycle substituted with 0-2 R^(4b), and (CR³R^(3a))_(r)5-10 memberedheterocycle consisting of carbon atoms and from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p) and substituted with 0-2R^(4b); R^(4d), at each occurrence, is selected from H, CH₂OR², OR²,C₁₋₄ alkyl, CH₂—CN, —CN, CH₂NO₂, NO₂, CH₂NR²R^(2a), NR²R^(2a),CH₂—C(O)R^(2c), C(O)R^(2c), NR²C(O)R^(2b), (CH₂)_(r)C(O)NR²R^(2a),NR²C(O)NR²R^(2a), (CH₂)_(r)SO₂NR²R^(2a), NR²SO₂NR²R^(2a), NR²SO₂R⁵,(CH₂)_(r)S(O)_(p)R^(5a), CH₂CF₃, CF₃, CH₂-5-6 membered carbocyclesubstituted with 0-1 R⁵, 5-6 membered carbocycle substituted with 0-1R⁵, a CH₂-5-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-1 R⁵, and a 5-6 membered heterocycle consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p) and substituted with 0-1 R⁵; R⁵, at each occurrence,is selected from H, ═O, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, OR³, CH₂OR³, F, Cl, —CN, NO₂,NR³R^(3a), CH₂NR³R^(3a), C(O)R³, CH₂C(O)R³, C(O)OR^(3c), CH₂C(O)OR^(3c),NR³C(O)R^(3a), C(O)NR³R^(3a), NR³C(O)NR³R^(3a), CH(═NOR^(3d)),C(═NR³)NR³R^(3a), NR³C(═NR³)NR³R^(3a), SO₂NR³R^(3a), NR³SO₂NR³R^(3a),NR³SO₂—C₁₋₄ alkyl, NR³SO₂CF₃, NR³SO₂-phenyl, S(O)_(p)CF₃, S(O)_(p)—C₁₋₄alkyl, S(O)_(p)-phenyl, CF₃, phenyl substituted with 0-2 R⁶, naphthylsubstituted with 0-2 R⁶, and benzyl substituted with 0-2 R⁶; R^(5a), ateach occurrence, is selected from CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃—, OR³, CH₂OR³,NR³R^(3a), CH₂NR³R^(3a), C(O)R³, CH₂C(O)R³, C(O)OR^(3c), CH₂C(O)OR^(3c),NR³C(O)R^(3a), CH₂NR³C(O)R^(3a), C(O)NR³R^(3a), CH₂C(O)NR³R^(3a), CF₃,CF₂CF₃, phenyl substituted with 0-2 R⁶, naphthyl substituted with 0-2R⁶, and benzyl substituted with 0-2 R⁶, provided that R^(5a) does notform a S—N or S(O)_(p)—C(O) bond; and R⁶, at each occurrence, isselected from H, OH, OR², F, Cl, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, CN, NO₂, NR²R^(2a),CH₂NR²R^(2a), C(O)R^(2b), CH₂C(O)R^(2b), NR²C(O)R^(2b),NR²C(O)NR²R^(2a), C(═NH)NH₂, NHC(═NH)NH₂, SO₂NR²R^(2a), NR²SO₂NR²R^(2a),and NR²SO₂C₁₋₄ alkyl.
 3. A compound according to claim 2, wherein thecompound is selected from:

P₄ is -G; M₄ is -A-B; G is substituted with 1 R^(a) and is selected fromthe following group, wherein R^(a) is attached adjacent to the point ofattachment of G:

R^(a) is R^(b)(CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₁R^(c); R^(b) is selectedfrom C(O)NR³, S(O)₂NR³, NR³C(O), and NR³S(O)₂; R^(c) is selected from H,OR³, NR³C(O)R³, C(O)NR³R^(3a), C₅₋₁₀ carbocycle substituted with 0-2 R⁴,and 5-10 membered heterocycle substituted with 0-2 R⁴ and consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p); provided that when the (CR⁸R^(2b))₀₋₄R^(b)₀₋₁(CR⁸R⁹)₀₋₁ portion of R^(a) is absent, then R^(c) is selected fromNR³C(O)R³, C₅₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-10 memberedheterocycle substituted with 0-2 R⁴ and consisting of: carbon atoms and1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p); further provided that the (CR⁸R^(2b))₀₋₄R^(b)₀₋₁(CR⁸R⁹)₀₋₄R^(c) portion of R^(a) is other than(CR⁸R^(2b))₀₋₃-unsubstituted-phenyl or (CR⁸R⁹)₀₋₃-unsubstituted-phenyl;G₁ is absent or is selected from (CR³R^(3a))₁₋₃, CR³═CR³,(CR³R^(3a))_(u)C(O)(CR³R^(3a))_(w), (CR³R^(3a))_(u)O(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)C(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)C(O)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)C(O)(CR³R^(3a))_(u)C(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(CR³R^(3a))_(w), (CR³R^(3a))_(u)S(O)(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(O)₂(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)S(O)₂(CR³R^(3a))_(w), and(CR³R^(3a))_(u)S(O)₂NR^(3b)(CR³R^(3a))_(w), wherein u+w total 0, 1, or2, wherein the right side of G₁ is attached to ring G, provided that G₁does not form a N—S, NCH₂N, NCH₂O, or NCH₂S bond with either group towhich it is attached; A is selected from one of the followingcarbocyclic and heterocyclic groups which are substituted with 0-2 R⁴;cyclohexyl, phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl,furanyl, morpholinyl, thienyl, pyrrolyl, pyrrolidinyl, oxazolyl,isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl,1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl,1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl,1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl,1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, benzofuranyl,benzothiofuranyl, indolinyl, indolyl, benzimidazolyl, benzoxazolyl,benzthiazolyl, indazolyl, benzisoxazolyl, benzisothiazolyl, andisoindazolyl; B¹ is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,—(CH₂)₀₋₁—C₅₋₆ carbocycle substituted with 0-2 R^(4b), and —(CH₂)₀₋₁-5-6membered heterocycle consisting of: carbon atoms and 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p) and substitutedwith 0-2 R^(4b); B² is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, C(O)R^(2e), C(O)NR^(2d)R^(2d), SO₂NR^(2d)R^(2d), andS(O)_(p)R^(5a); B³ is selected from H, C₁₋₆ alkyl substituted with 0-1R^(4c), —(CH₂)₀₋₁-3-6 membered carbocycle substituted with 0-1 R⁵, and a—(CH₂)₀₋₁-5-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-1 R⁵; B⁴ is selected from H, SO₂R^(3b) and OR²; B⁵ isNR²R^(2f); ring Q is a 5-6 membered ring consisting of, in addition tothe N—CR⁴—N group shown, carbon atoms and 0-2 heteroatoms selected fromN, O, and S(O)_(p), and the ring is substituted with an additional 0-2R^(4d); Q⁴ is selected from C═O and SO₂; ring Q³ is a 5-7 membered ringconsisting of, in addition to the N-Q⁴ group shown, carbon atoms and 0-2heteroatoms selected from NR^(4c), O, S, S(O), and S(O)₂, wherein: 0-2double bonds are present within the ring and the ring is substitutedwith 0-2 R^(4a); alternatively, ring Q³ is a 5-7 membered ring to whichanother ring is fused, wherein: the 5-7 membered ring consists of, inaddition to the shown amide group, carbon atoms and 0-2 heteroatomsselected from NR^(4c), O, S, S(O), and S(O)₂, and 0-1 double bonds arepresent within the ring; the fusion ring is phenyl or a 5-6 memberedheteroaromatic consisting of carbon atoms and 1-2 heteroatoms selectedfrom NR^(4c), O, and S; ring Q³, which includes the 5-7 membered ringand the fusion ring, is substituted with 0-3 R^(4a); ring Q⁵, is a C₃₋₆monocyclic carbocycle or 5-6 membered monocyclic heterocycle, whereinthe carobocycle or heterocycle consists of carbon atoms and 0-2heteroatoms selected from N, O, and S(O)_(p), the carbocycle orheterocycle further comprises 0-1 double bonds and 0-1 carbonyl groups,and the carbocycle or heterocycle is substituted with 0-2 R⁴; X isselected from —(CR²R^(2a))₁₋₂—, —C(═NR^(1b))—, —C(O)—, —S(O)₂—,—NR²S(O)₂—, —NR²S(O)₂—, —NR²C(O)—, —C(O)NR²—, —NR²C(O)CR²R^(2a)—,—NR²C(O)NR²—, NR², —NR²CR²R^(2a)—, —CR²R^(2a)NR²—, O, —OCR²R^(2a)—, and—CR²R^(2a)O—; Y is selected from: CY¹Y²R^(4a), NR³R^(3a), andC(O)NR³R^(3a); Y¹ and Y² are independently C₁₋₂ alkyl substituted with0-2 R⁴; alternatively, Y is selected from one of the followingcarbocyclic and heterocycles that are substituted with 1 R^(4a) and 0-1R⁴: cyclopentyl, cyclohexyl, phenyl, piperidinyl, piperazinyl, pyridyl,pyrimidyl, furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl,oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl,oxadiazole, thiadiazole, triazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole,1,2,5-oxadiazole, 1,3,4-oxadiazole, 1,2,3-thiadiazole,1,2,4-thiadiazole, 1,2,5-thiadiazole, 1,3,4-thiadiazole, 1,2,3-triazole,1,2,4-triazole, 1,2,5-triazole, 1,3,4-triazole, benzofuran,benzothiofuran, indole, benzimidazole, benzimidazolone, benzoxazole,benzthiazole, indazole, benzisoxazole, benzisothiazole, and isoindazole;R^(1a) is selected from H, R^(1b), CH(CH₃)R^(1b), C(CH₃)₂R^(1b),CH₂R^(1b), and CH₂CH₂R^(1b), provided that R^(1a) forms other than anN-halo, N—S, or N—CN bond; alternatively, when two R^(1a) groups areattached to adjacent atoms, together with the atoms to which they areattached they form a 5-6 membered ring consisting of: carbon atoms and0-2 heteroatoms selected from the group consisting of N, O, andS(O)_(p), this ring being substituted with 0-2 R^(4b) and 0-3 ringdouble bonds; R^(1b) is selected from H, CH₃, CH₂CH₃, F, Cl, Br, —CN,—CHO, CF₃, OR², NR²R^(2a), C(O)R^(2b), CO₂R^(2b), OC(O)R², CO₂R^(2a),S(O)_(p)R², NR²(CH₂)_(r)OR², NR²C(O)R^(2b), C(O)NR²R^(2a), SO₂NR²R^(2a),NR²SO₂R², phenyl substituted with 0-2 R^(4b), and 5-6 membered aromaticheterocycle consisting of carbon atoms and from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-2 R^(4b), provided that R^(1b) forms other than an O—O, N-halo, N—S,or N—CN bond; R², at each occurrence, is selected from H, CF₃, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, phenyl substituted with 0-2 R^(4b), abenzyl substituted with 0-2 R^(4b), and a 5-6 membered aromaticheterocycle consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-2 R^(4b); R^(2a), at each occurrence, is selected from H, CF₃, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzyl substituted with 0-2 R^(4b), phenylsubstituted with 0-2 R^(4b), and 5-6 membered aromatic heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p), and substituted with 0-2 R^(4b);alternatively, NR²R^(2a) forms a 5 or 6 membered saturated, partiallysaturated or unsaturated ring substituted with 0-2 R^(4b) and consistingof: 0-1 additional heteroatoms selected from the group consisting of N,O, and S(O)_(p); R^(2b), at each occurrence, is selected from CF₃, C₁₋₄alkoxy, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzyl substituted with 0-2R^(4b), phenyl substituted with 0-2 R^(4b), and 5-6 membered aromaticheterocycle consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-2 R^(4b); R^(2c), at each occurrence, is selected from CF₃, OH, OCH₃,OCH₂CH₃, OCH₂CH₂CH₃, OCH(CH₃)₂, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzylsubstituted with 0-2 R^(4b), phenyl substituted with 0-2 R^(4b), and 5-6membered aromatic heterocycle containing from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-2 R^(4b); R^(2d), at each occurrence, is selected from H, R^(4c), C₁₋₄alkyl substituted with 0-2 R^(4c), C₃₋₆ carbocycle substituted with 0-2R^(4c), —(CR³R^(3a))—C₃₋₆ carbocycle substituted with 0-2 R^(4c), 5-6membered heterocycle substituted with 0-2 R^(4c) and consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p), and —(CR³R^(3a))-5-6 membered heterocyclesubstituted with 0-2 R^(4c) and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),provided that R^(2d) forms other than a N-halo, N—C-halo, S(O)_(p)-halo,O-halo, N—S, S—N, S(O)_(p)—S(O)_(p), S—O, O—N, O—S, or O—O moiety;R^(2e), at each occurrence, is selected from H, R^(4c), C₁₋₄ alkylsubstituted with 0-2 R^(4c), C₃₋₆ carbocycle substituted with 0-2R^(4c), —(CR³R^(3a))—C₃₋₆ carbocycle substituted with 0-2 R^(4c), 5-6membered heterocycle substituted with 0-2 R^(4c) and consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p), and —(CR³R^(3a))-5-6 membered heterocyclesubstituted with 0-2 R^(4c) and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),provided that R^(2e) forms other than a C(O)-halo or C(O)—S(O)_(p)moiety; R^(2f), at each occurrence, is selected from H, CF₃, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, OCH₃, and benzyl; alternatively, NR²R^(2f)forms a 5-6 membered ring consisting of: carbon atoms and 0-2 additionalheteroatoms selected from N, O, and S(O)_(p), and this ring issubstituted with 0-2 R^(4b); alternatively, B⁴ and R^(2f) combine toform a 5-6 membered ring consisting of: carbon atoms and 0-1 additionalheteroatoms selected from N, O, and S(O)_(p), and this ring issubstituted with 0-2 R^(4b) and the R² group of NR²R^(2f), in additionto the groups recited below, can be SO₂R^(3b); R^(3b), at eachoccurrence, is selected from H, CF₃, CH₃, CH₂CH₃, CH₂CH₂CH₃, andCH(CH₃)₂; R⁴, at each occurrence, is selected from H, ═O, CH₂OR²,(CH₂)₂OR², OR², F, Cl, Br, I, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, —CN, NO₂, NR²R^(2a),CH₂NR²R^(2a), (CH₂)₂NR²R^(2a), C(O)R^(2c), NR²C(O)R^(2b), C(O)NR²R^(2a),NR²C(O)NR²R^(2a), SO₂NR²R^(2a), CF₃, and CF₂CF₃; R^(4a) is selected from—(CR³R^(3g))_(r)-5-6 membered carbocycle substituted with 0-3 R^(4c),—(CR³R³⁹)_(r)-5-6 membered heterocycle substituted with 0-3 R^(4c) andconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p), (CR³R^(3g))_(r)NR^(2d)R^(2d),(CR³R^(3g))_(r)N(→O)R^(2d)R^(2d), (CR³R^(3g))_(r)OR^(2d),(CR³R^(3g))_(r)—NR^(2d)C(O)R^(2e), (CR³R^(3g))_(r)—C(O)R^(2e),(CR³R^(3g))_(r)—OC(O)R^(2e), (CR³R^(3g))_(r)—C(O)NR^(2d)R^(2d),(CR³R^(3g))_(r)—C(O)OR^(2d), (CR³R^(3g))_(r)—NR^(2d)C(O)NR^(2d)R^(2d),(CR³R^(3g))_(r)—NR^(2d)C(O)OR^(2d), (CR³R^(3g))_(r)—SO₂NR^(2d)R^(2d),(CR³R^(3g))_(r)—NR^(2d)SO₂R^(2d), and (CR³R^(3g))_(r)—S(O)_(p)R^(2d),provided that S(O)_(p)R^(2d) forms other than S(O)₂H or S(O)H; R^(4b),at each occurrence, is selected from H, ═O, OR³, CH₂OR³, F, Cl, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, —CN, NO₂, NR³R^(3a), CH₂NR³R^(3a), C(O)R³,CH₂—C(O)R³, C(O)OR^(3c), CH₂—C(O)OR^(3c), NR³C(O)R^(3a),CH₂NR³C(O)R^(3a), C(O)NR³R^(3a), CH₂—C(O)NR³R^(3a), SO₂NR³R^(3a),CH₂SO₂NR³R^(3a), NR³SO₂—C₁₋₄ alkyl, CH₂NR³SO₂—C₁₋₄ alkyl, NR³SO₂-phenyl, CH₂NR³SO₂-phenyl, S(O)_(p)CF₃, CH₂S(O)_(p)CF₃, S(O)_(p)—C₁₋₄alkyl, CH₂S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl, CH₂S(O)_(p)-phenyl, andCF₃; R^(4c), at each occurrence, is selected from ═O, OR²,(CR³R^(3a))OR², F, (CR³R^(3a))F, Br, (CR³R^(3a))Br, Cl, (CR³R^(3a))Cl,CF₃, (CR³R^(3a))CF₃, C₂₋₃ alkenyl, C₂₋₃ alkynyl, C₁₋₄ alkyl, —CN,(CR³R^(3a))CN, NO₂, (CR³R^(3a))NO₂, NR²R^(2a), (CR³R^(3a))NR²R^(2a),N(→O)R²R^(2a), (CR³R^(3a))N(→O)R²R^(2a), C(O)R^(2c),(CR³R^(3a))C(O)R^(2c), NR²C(O)R^(2b), (CR³R^(3a))NR²C(O)R^(2b),C(O)NR²R^(2a), (CR³R^(3a))C(O)NR²R^(2a), NR²C(O)NR²R^(2a),(CR³R^(3a))NR²C(O)NR²R^(2a), SO₂NR²R^(2a), (CR³R^(3a))SO₂NR²R^(2a),NR²SO₂NR²R^(2a), (CR³R^(3a))NR²SO₂NR²R^(2a), NR²SO₂R^(5a),(CR³R^(3a))NR²SO₂R^(5a), S(O)_(p)R^(5a), (CR³R^(3a))S(O)_(p)R^(5a), CF₃,CF₂CF₃, C₃₋₁₀ carbocycle substituted with 0-2 R^(4b), (CR³R^(3a))C₃₋₁₀carbocycle substituted with 0-2 R^(4b), 5-10 membered heterocycleconsisting of carbon atoms and from 1-4 heteroatoms selected from thegroup consisting of N, O, and S(O)_(p) and substituted with 0-2 R^(4b),and (CR³R^(3a))-5-10 membered heterocycle consisting of carbon atoms andfrom 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p) and substituted with 0-2 R^(4b); R^(4d), at each occurrence, isselected from H, CH₂OR², OR², CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, —CN, NO₂,CH₂NR²R^(2a), NR²R^(2a), C(O)R^(2c), NR²C(O)R^(2b), C(O)NR²R^(2a),NR²C(O)NR²R^(2a), NR²SO₂R⁵, SO₂NR²R^(2a), 6-membered carbocyclesubstituted with 0-1 R⁵, and a 5-6 membered heterocycle consisting of:carbon atoms and 1-2 heteroatoms selected from the group consisting ofN, O, and S(O)_(p) and substituted with 0-1 R⁵; R⁵, at each occurrence,is selected from H, ═O, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, OR³, CH₂OR³,F, Cl, —CN, NO₂, NR³R^(3a), CH₂NR³R^(3a), C(O)R³, CH₂C(O)R³,C(O)OR^(3c), CH₂C(O)OR^(3c), NR³C(O)R^(3a), C(O)NR³R^(3a), SO₂NR³R^(3a),NR³SO₂—C₁₋₄ alkyl, NR³SO₂CF₃, NR³SO₂-phenyl, S(O)_(p)CF₃, S(O)_(p)—C₁₋₄alkyl, S(O)_(p)-phenyl, CF₃, phenyl substituted with 0-2 R⁶, naphthylsubstituted with 0-2 R⁶, and benzyl substituted with 0-2 R⁶; and R⁶, ateach occurrence, is selected from H, OH, OR², F, Cl, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, —CN, NO₂, NR²R^(2a), CH₂NR²R^(2a), C(O)R^(2b),CH₂C(O)R^(2b), NR²C(O)R^(2b), SO₂NR²R^(2a), and NR²SO₂C₁₋₄ alkyl.
 4. Acompound according to claim 3, wherein: G is substituted with 1 R^(a),wherein R^(a) is attached adjacent to the point of attachment of G:R^(a) is R^(b)(CR⁸R^(2b))₀₋₃R^(b) ₀₋₁R^(c); R^(b) is C(O)NR³; R^(c) isselected from H, OR³, C₅₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-10membered heterocycle substituted with 0-2 R⁴ and consisting of: carbonatoms and 1-4 heteroatoms selected from the group consisting of N, O,and S(O)_(p); provided that when the (CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₁portion of R^(a) is absent, then R^(c) is selected from C₅₋₁₀ carbocyclesubstituted with 0-2 R⁴ and 5-11 membered heterocycle substituted with0-2 R⁴ and consisting of: carbon atoms and 1-4 heteroatoms selected fromthe group consisting of N, O, and S(O)_(p); further provided that the(CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₄R^(c) portion of R^(a) is other than(CR⁸R^(2b))₀₋₃-unsubstituted-phenyl or (CR⁸R⁹)₀₋₃-unsubstituted-phenyl;G₁ is absent or is selected from CH₂, CH₂CH₂, CH₂O, OCH₂, NH, CH₂NH,NHCH₂, CH₂C(O), C(O)CH₂, C(O)NH, NHC(O), CH₂S(O)₂, S(O)₂(CH₂), SO₂NH,and NHSO₂, wherein the right side of G₁ is attached to ring G, providedthat G₁ does not form a N—S, NCH₂N, NCH₂O, or NCH₂S bond with eithergroup to which it is attached; A is selected from cyclohexyl,piperidinyl, piperazinyl, phenyl, pyridyl, and pyrimidyl, and issubstituted with 0-2 R⁴; B is selected from Y,N(B¹)C(O)C(R³R^(3g))NB²B³,

provided that Z and B are attached to different atoms on A, the R^(4d)shown is other than OH, and that the A-X—N moiety forms other than aN—N—N group; B¹ is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, andCH(CH₃)₂; B² is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, and CH(CH₃)₂;B³ is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, C₂₋₅ alkyl substituted with 1R^(4c), —(CH₂)₀₋₁-3-6 membered carbocycle substituted with 0-1 R⁵, and a—(CH₂)₀₋₁-5-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-1 R⁵; B⁴ is selected from H, SO₂R^(3b), and OR²; B⁵is NR²R^(2f); ring Q is a 5-6 membered ring consisting of, in additionto the N—CR^(4d)═N group shown, carbon atoms and 0-1 heteroatomsselected from N, O, and S(O)_(p), and the ring is substituted with anadditional 0-2 R^(4d); Q⁴ is selected from C═O and SO₂; ring Q³ is a 6-7membered ring consisting of, in addition to the N-Q⁴ group shown, carbonatoms and 0-1 heteroatoms selected from NR^(4c), O, S, S(O), and S(O)₂,wherein: 0-2 double bonds are present within the ring and the ring issubstituted with 0-2 R⁴; alternatively, ring Q³ is a 5-7 membered ringto which another ring is fused, wherein: the 5-7 membered ring consistsof, in addition to the shown amide group, carbon atoms and 0-1heteroatoms selected from NR^(4c), O, S, S(O), and S(O)₂, and 0-1 doublebonds are present within the ring; the fusion ring is phenyl; ring Q³,which includes the 5-7 membered ring and the fusion ring, is substitutedwith 0-2 R⁴; ring Q⁵ is substituted with 0-1 R⁴ and is selected fromcyclopropyl, cyclobutyl, cyclopentyl, cyclopentanonyl, cyclohexyl,cyclohexanonyl, pyrrolidinyl, pyrrolidinonyl, piperidinyl,piperidinonyl, tetrahydrofuranyl, and tetrahydropyranyl; X is selectedfrom CH₂, C(O), —S(O)₂—, —NHC(O)—, —C(O)NH—, —CH₂NH—, O, and —CH₂O—; Yis selected from N(CH₃)₂, C(O)(CH₃)₂, C(CH₃)₂R^(4a) andC(CH₂CH₃)₂R^(4a); altneratively, Y is selected from phenyl, pyridyl,pyrrolidino, N-pyrrolidino-carbonyl, morpholino, N-morpholino-carbonyl,1,2,3-triazolyl, imidazolyl, and benzimidazolyl, and is substituted with1 R^(4a) and 0-1 R⁴; R^(1a), at each occurrence, is selected from H,R^(1b), CH(CH₃)R^(1b), C(CH₃)₂R^(1b), and CH₂R^(1b), provided thatR^(1a) forms other than an N-halo, N—S, or N—CN bond; R^(1b) is selectedfrom CH₃, CH₂CH₃, F, Cl, Br, —CN, CF₃, OR², NR²R^(2a), C(O)R^(2b),CO₂R^(2b), CO₂R^(2a), S(O)_(p)R², C(O)NR²R^(2a), SO₂NR²R^(2a), NR²SO₂R²,and 5-6 membered aromatic heterocycle consisting of carbon atoms andfrom 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), and substituted with 0-2 R^(4b), provided that R^(1b) formsother than an O—O, N-halo, N—S, or N—CN bond; R², at each occurrence, isselected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, phenyl substitutedwith 0-1 R^(4b), benzyl substituted with 0-1 R^(4b), and 5-6 memberedaromatic heterocycle consisting of: carbon atoms and 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p), andsubstituted with 0-1 R^(4b); R^(2a), at each occurrence, is selectedfrom H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzyl substituted with 0-1R^(4b), phenyl substituted with 0-1 R^(4b), and 5-6 membered aromaticheterocycle consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-1 R^(4b); alternatively, NR²R^(2a) forms a 5 or 6 membered saturated,partially saturated or unsaturated ring substituted with 0-1 R^(4b) andconsisting of: 0-1 additional heteroatoms selected from the groupconsisting of N, O, and S(O)_(p); R^(2b), at each occurrence, isselected from OCH₃, OCH₂CH₃, OCH₂CH₂CH₃, OCH(CH₃)₂, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, benzyl substituted with 0-1 R^(4b), phenylsubstituted with 0-1 R^(4b), and 5-6 membered aromatic heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p), and substituted with 0-1 R^(4b);R^(2c), at each occurrence, is selected from OH, OCH₃, OCH₂CH₃,OCH₂CH₂CH₃, OCH(CH₃)₂, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzylsubstituted with 0-1 R^(4b), phenyl substituted with 0-1 R^(4b), and 5-6membered aromatic heterocycle containing from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-1 R^(4b); R^(2d), at each occurrence, is selected from H, R^(4c), C₁₋₄alkyl substituted with 0-2 R^(4c), C₃₋₆ carbocycle substituted with 0-2R^(4c), —(CH₂)—C₃₋₆ carbocycle substituted with 0-2 R^(4c), 5-6 memberedheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), and —(CH₂)-5-6 membered heterocycle substituted with 0-2R^(4c) and consisting of: carbon atoms and 1-4 heteroatoms selected fromthe group consisting of N, O, and S(O)_(p), provided that R^(2d) formsother than a N-halo, N—C-halo, S(O)_(p)-halo, O-halo, N—S, S—N,S(O)_(p)—S(O)_(p), S—O, O—N, O—S, or O—O moiety; R^(2e), at eachoccurrence, is selected from H, R^(4c), C₁₋₄ alkyl substituted with 0-2R^(4c), C₃₋₆ carbocycle substituted with 0-2 R^(4c), —(CH₂)—C₃₋₆carbocycle substituted with 0-2 R^(4c), 5-6 membered heterocyclesubstituted with 0-2 R^(4c) and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),and —(CH₂)-5-6 membered heterocycle and consisting of: carbon atoms and1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), provided that R^(2e) forms other than a C(O)-halo orC(O)—S(O)_(p) moiety; R^(2f), at each occurrence, is selected from H,CH₃, CH₂CH₃, OCH₃, and benzyl; alternatively, NR²R^(2f) forms a 5-6membered ring consisting of: carbon atoms and 0-1 additional heteroatomsselected from N, O, and S(O)_(p), and this ring is substituted with 0-1R^(4b); alternatively, B⁴ and R^(2f) combine to form a 5 membered ringconsisting of: carbon atoms and 0-1 additional heteroatoms selected fromN, O, and S(O)_(p), and this ring is substituted with 0-2 R^(4b) and theR² group of NR²R^(2f), in addition to the groups recited below, can beSO₂R^(3b); R^(3b), at each occurrence, is selected from H and CH₃; R⁴,at each occurrence, is selected from H, ═O, OH, OR², CH₂OR², (CH₂)₂OR²,F, Br, Cl, I, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, NR²R^(2a), CH₂NR²R^(2a),(CH₂)₂NR²R^(2a), C(O)R^(2c), NR²C(O)R^(2b), C(O)NR²R^(2a), SO₂NR²R^(2a),CF₃, and CF₂CF₃; R^(4a) is selected from —(CR³R^(3g))_(r)-5-6 memberedcarbocycle substituted with 0-3 R^(4c), —(CR³R^(3g))_(r)-5-6 memberedheterocycle substituted with 0-3 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), (CR³R^(3g))_(r)NR^(2d)R^(2d),(CR³R^(3g))_(r)N(→O)R^(2d)R^(2d), (CR³R^(3g))_(r)OR^(2d),(CR³R^(3g))_(r)—C(O)NR^(2d)R^(2d), (CR³R^(3g))_(r)—NR^(2d)C(O)R^(2e),(CR³R^(3g))_(r)—C(O)R^(2e), (CR³R^(3g))_(r)—NR^(2d)C(O)NR^(2d)R^(2d),(CR³R^(3g))_(r)—NR^(2d)C(O)OR^(2d), (CR³R^(3g))_(r)—NR^(2d)SO₂R^(2d),and (CR³R^(3g))_(r)—S(O)_(p)R^(2d), provided that S(O)_(p)R^(2d) formsother than S(O)₂H or S(O)H; R^(4b), at each occurrence, is selected fromH, ═O, OR³, CH₂OR³, F, Cl, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, —CN, NO₂,NR³R^(3a), CH₂NR³R^(3a), C(O)R³, C(O)OR^(3c), NR³C(O)R^(3a),C(O)NR³R^(3a), SO₂NR³R^(3a), NR³SO₂—C₁₋₄ alkyl, NR³SO₂-phenyl,S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl, and CF₃; R^(4c), at eachoccurrence, is selected from ═O, OR², CH₂OR², F, Br, Cl, CF₃, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃,C(CH₃)₃, C₂₋₃ alkenyl, C₂₋₃ alkynyl, —CN, NO₂, NR²R^(2a), CH₂NR²R^(2a),N(→O)R²R^(2a), CH₂N(→O)R²R^(2a), C(O)R^(2c), CH₂C(O)R^(2c),NR²C(O)R^(2b), CH₂NR²C(O)R^(2b), C(O)NR²R^(2a), CH₂C(O)NR²R^(2a),SO₂NR²R^(2a), CH₂SO₂NR²R^(2a), NR²SO₂R^(5a), CH₂NR²SO₂R^(5a),S(O)_(p)R^(5a), CH₂S(O)_(p)R^(5a), CF₃, CF₂CF₃, C₃₋₆ carbocyclesubstituted with 0-2 R^(4b), (CH₂)C₃₋₆ carbocycle substituted with 0-2R^(4b), 5-6 membered heterocycle consisting of carbon atoms and from 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-2 R^(4b), and (CH₂)-5-6 membered heterocycleconsisting of carbon atoms and from 1-4 heteroatoms selected from thegroup consisting of N, O, and S(O)_(p) and substituted with 0-2 R^(4b);R^(4d), at each occurrence, is selected from H, CH₂OR², OR², CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃,C(CH₃)₃, CH₂NR²R^(2a), NR²R^(2a), C(O)R^(2c), NR²C(O)R^(2b),C(O)NR²R^(2a), SO₂NR²R^(2a), NR²SO₂R⁵, phenyl substituted with 0-1 R⁵,and a 5-6 membered heterocycle consisting of: carbon atoms and 1heteroatom selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-1 R⁵; R⁵, at each occurrence, is selected from H, ═O,CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, OR³, CH₂OR³, F, Cl, —CN, NO₂,NR³R^(3a), CH₂NR³R^(3a), C(O)R³, C(O)OR^(3c), NR³C(O)R^(3a),C(O)NR³R^(3a), SO₂NR³R^(3a), NR³SO₂—C₁₋₄ alkyl, NR³SO₂-phenyl,S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl, CF₃, phenyl substituted with 0-2R⁶, naphthyl substituted with 0-2 R⁶, and benzyl substituted with 0-2R⁶; and R⁶, at each occurrence, is selected from H, OH, OR², F, Cl, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, —CN, NO₂, NR²R^(2a), CH₂NR²R^(2a),C(O)R^(2b), CH₂C(O)R^(2b), NR²C(O)R^(2b), and SO₂NR²R^(2a).
 5. Acompound according to claim 4, wherein: A is selected from the group:cyclohexyl, phenyl, 2-pyridyl, 3-pyridyl, 2-pyrimidyl, 2-Cl-phenyl,3-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 2-methylphenyl, 2-aminophenyl, and2-methoxyphenyl; B is selected from Y, N(B¹)C(O)C(R³R^(3g))NB²B³,

provided that Z and B are attached to different atoms on A and that theR^(4d) shown is other than OH; B¹ is selected from H, CH₃, CH₂CH₃, andCH₂CH₂CH₃; B² is selected from H, CH₃, and CH₂CH₃; B³ is selected fromCH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, C(CH₃)₃,CH(CH₃)CH₂CH(CH₃)₂, CH₂CH₂OH, CH(CH₃)CH₂OH, CH(phenyl)CH₂CH₃,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and CH₂-cyclopropyl;

is attached to a different atom on A than M and is selected from thegroup:

ring Q⁵ is selected from cyclopropyl, cyclobutyl, cyclopentyl,2-cyclopentanonyl, cyclohexyl, 2-cyclohexanonyl, pyrrolidinyl (attachedto A and R^(4a) at the 2-position), pyrrolidinyl (attached to A andR^(4a) at the 3-position), 2-pyrrolidinonyl (attached to A and R^(4a) atthe 3-position), piperidinyl (attached to A and R^(4a) at the4-position), 4-piperdinonyl (attached to A and R^(4a) at the3-position), tetrahydrofuranyl, and tetrahydropyranyl (attached to A andR^(4a) at the 4-position); Y is selected from N(CH₃)₂, C(O)(CH₃)₂,C(CH₃)₂R^(4a) and C(CH₂CH₃)₂R^(4a); alternatively, Y is selected fromphenyl, pyridyl, 1,2,3-triazolyl, imidazolyl, and benzimidazolyl, and issubstituted with 1 R^(4a); R^(1a), at each occurrence, is selected fromH, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH₂F, CH₂Cl, Br, CH₂Br, —CN, CH₂CN, CF₃,CH₂CF₃, OCH₃, CH₂OH, C(CH₃)₂OH, CH₂OCH₃, NH₂, CH₂NH₂, NHCH₃, CH₂NHCH₃,N(CH₃)₂, CH₂N(CH₃)₂, CO₂H, COCH₃, CO₂CH₃, CH₂CO₂CH₃, SCH₃, CH₂SCH₃,S(O)CH₃, CH₂S(O)CH₃, S(O)₂CH₃, CH₂S(O)₂CH₃, C(O)NH₂, CH₂C(O)NH₂, SO₂NH₂,CH₂SO₂NH₂, NHSO₂CH₃, CH₂NHSO₂CH₃, pyridin-2-yl, pyridin-3-yl,pyridin-4-yl, pyridin-2-yl-N-oxide, pyridin-3-yl-N-oxide,pyridin-4-yl-N-oxide, imidazol-1-yl, CH₂-imidazol-1-yl,4-methyl-oxazol-2-yl, 4-N,N-dimethylaminomethyl-oxazol-2-yl,1,2,3,4-tetrazol-1-yl, 1,2,3,4-tetrazol-5-yl, CH₂-1,2,3,4-tetrazol-1-yl,and CH₂-1,2,3,4-tetrazol-5-yl, provided that R^(1a) forms other than anN-halo, N—S, or N—CN bond; R², at each occurrence, is selected from H,CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, phenyl substituted with 0-1 R^(4b),benzyl substituted with 0-1 R^(4b), and 5 membered aromatic heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p), and substituted with 0-1 R^(4b);R^(2a), at each occurrence, is selected from H, CH₃, and CH₂CH₃;alternatively, NR²R^(2a) forms a 5 or 6 membered saturated, partiallysaturated or unsaturated ring substituted with 0-1 R^(4b) and consistingof: 0-1 additional heteroatoms selected from the group consisting of N,O, and S(O)_(p); R^(2b), at each occurrence, is selected from OCH₃,OCH₂CH₃, CH₃, and CH₂CH₃; R^(2c), at each occurrence, is selected fromOH, OCH₃, OCH₂CH₃, CH₃, and CH₂CH₃; R^(2d), at each occurrence, isselected from H, R^(4c), C₁₋₄ alkyl substituted with 0-2 R^(4c), C₃₋₆cycloalkyl substituted with 0-2 R^(4c), phenyl substituted with 0-2R^(4c), and 5-6 membered aromatic heterocycle substituted with 0-2R^(4c) and consisting of: carbon atoms and 1-4 heteroatoms selected fromthe group consisting of N, O, and S(O)_(p), provided that R^(2d) formsother than a N-halo, N—C-halo, S(O)_(p)-halo, O-halo, N—S, S—N,S(O)_(p)—S(O)_(p), S—O, O—N, O—S, or O—O moiety; R^(2e), at eachoccurrence, is selected from H, R^(4c), C₁₋₄ alkyl substituted with 0-2R^(4c), C₃₋₆ cycloalkyl substituted with 0-2 R^(4c), phenyl substitutedwith 0-2 R^(4c), and 5-6 membered aromatic heterocycle substituted with0-2 R^(4c) and consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), provided that R^(2e)forms other than a C(O)-halo or C(O)—S(O)_(p) moiety; R^(2f), at eachoccurrence, is selected from H, CH₃, CH₂CH₃, and OCH₃; alternatively,NR²R^(2f) forms a ring selected from morpholine, piperazine, piperidine,and pyrrolidine; R⁴, at each occurrence, is selected from H, ═O, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃,and C(CH₃)₃; R^(4a) is selected from —(CH₂)_(r)-5-6 membered carbocyclesubstituted with 0-3 R^(4c), —(CH₂)_(r)-5-6 membered heterocyclesubstituted with 0-3 R^(4c) and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),(CH₂)_(r)NR^(2d)R^(2d), (CH₂)_(r)N(→O)R^(2d)R^(2d), (CH₂)_(r)OR^(2d),(CH₂)_(r)—C(O)NR^(2d)R^(2d), (CH₂)_(r)—NR^(2d)C(O)R^(2e),(CH₂)_(r)—C(O)R^(2e), (CH₂)_(r)—NR^(2d)C(O)NR^(2d)R^(2d),(CH₂)_(r)—NR^(2d)C(O)OR^(2d), (CH₂)_(r)—NR^(2d)SO₂R^(2d), and(CH₂)_(r)—S(O)_(p)R^(2d), provided that S(O)_(p)R^(2d) forms other thanS(O)₂H or S(O)H; R^(4b), at each occurrence, is selected from H, ═O,OR³, CH₂OR³, F, Cl, CH₃, CH₂CH₃, NR³R^(3a), CH₂NR³R^(3a), C(O)R³,C(O)OR^(3c), NR³C(O)R^(3a), C(O)NR³R^(3a), SO₂NR³R^(3a), NR³SO₂-phenyl,S(O)₂CH₃, S(O)₂-phenyl, and CF₃; R^(4c), at each occurrence, is selectedfrom ═O, OH, OCH₃, OCH₂CH₃, OCH₂CH₂CH₃, OCH(CH₃)₂, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, C₂₋₃ alkenyl, C₂₋₃ alkynyl, CH₂OH, CH₂OCH₃,CH₂OCH₂CH₃, CH₂OCH₂CH₂CH₃, CH₂OCH(CH₃)₂, F, Br, Cl, CF₃, NR²R^(2a),CH₂NR²R^(2a), N(→O)R²R^(2a), CH₂N(→O)R²R^(2a), C(O)R^(2c),CH₂C(O)R^(2c), NR²C(O)R^(2b), CH₂NR²C(O)R^(2b), C(O)NR²R^(2a),CH₂C(O)NR²R^(2a), SO₂NR²R^(2a), CH₂SO₂NR²R^(2a), NR²SO₂R^(5a),CH₂NR²SO₂R^(5a), S(O)_(p)R^(5a), CH₂S(O)_(p)R^(5a), CF₃, cyclopropylsubstituted with 0-1 R^(4b), cyclobutyl substituted with 0-1 R^(4b),cyclopentyl substituted with 0-1 R^(4b), phenyl substituted with 0-1R^(4b), —CH₂-cyclopropyl substituted with 0-1 R^(4b), —CH₂-cyclobutylsubstituted with 0-1 R^(4b), —CH₂-cyclopentyl substituted with 0-1R^(4b), benzyl substituted with 0-2 R^(4b), 5-6 membered aromaticheterocycle consisting of carbon atoms and from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p) and substituted with 0-2R^(4b), and (CH₂)-5-6 membered aromatic heterocycle consisting of carbonatoms and from 1-4 heteroatoms selected from the group consisting of N,O, and S(O)_(p) and substituted with 0-2 R^(4b); R^(4d), at eachoccurrence, is selected from H, OCH₃, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,NR²R^(2a), NR²C(O)R^(2b), NR²SO₂R⁵, phenyl, 2-oxo-pyrrolidinyl, and2-oxo-piperidinyl; R⁵, at each occurrence, is selected from H, ═O, CH₃,CH₂CH₃, OR³, CH₂OR³, F, Cl, NR³R^(3a), CH₂NR³R^(3a), C(O)R³,C(O)OR^(3c), NR³C(O)R^(3a), C(O)NR³R^(3a), SO₂NR³R^(3a), NR³SO₂—C₁₋₄alkyl, NR³SO₂-phenyl, S(O)₂—CH₃, S(O)₂-phenyl, CF₃, phenyl substitutedwith 0-2 R⁶, naphthyl substituted with 0-2 R⁶, and benzyl substitutedwith 0-2 R⁶; and R⁶, at each occurrence, is selected from H, OH, OR², F,Cl, CH₃, CH₂CH₃, NR²R^(2a), CH₂NR²R^(2a), C(O)R^(2b), CH₂C(O)R^(2b),NR²C(O)R^(2b), and SO₂NR²R^(2a).
 6. A compound according to claim 5,wherein: A is selected from the group: phenyl, 2-pyridyl, 2-pyrimidyl,and 2-F-phenyl, wherein B is substituted at the 4-position of A; B isselected from:

R^(2d), at each occurrence, is selected from H, C₁₋₄ alkyl substitutedwith 0-1 R^(4c), C₃₋₆ cycloalkyl substituted with 0-2 R^(4c), phenylsubstituted with 0-2 R^(4c), and a 5-6 membered aromatic heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p), provided that R^(2d) forms other thana N-halo, N—C-halo, S(O)_(p)-halo, O-halo, N—S, S—N, S(O)_(p)—S(O)_(p),S—O, O—N, O—S, or O—O moiety; R^(2e), at each occurrence, is selectedfrom H, C₁₋₄ alkyl substituted with 0-1 R^(4c), C₃₋₆ cycloalkylsubstituted with 0-2 R^(4c), phenyl, substituted with 0-2 R^(4c), and5-6 membered aromatic heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),provided that R^(2e) forms other than a C(O)-halo or C(O)—S(O)_(p)moiety; R^(4a) is selected from NR^(2d)R^(2d), CH₂NR^(2d)R^(2d),CH₂CH₂NR^(2d)R^(2d), N(→O)R^(2d)R^(2d), CH₂N(→O)R^(2d)R^(2d),CH₂OR^(2d), C(O)R^(2e), C(O)NR^(2d)R^(2d), CH₂C(O)NR^(2d)R^(2d),NR^(2d)C(O)R^(2e), CH₂NR^(2d)C(O)R^(2e), NR^(2d)C(O)NR^(2d)R^(2d),CH₂NR^(2d)C(O)NR^(2d)R^(2d), NR^(2d)C(O)OR^(2d), CH₂NR^(2d)C(O)OR^(2d),NR^(2d)SO₂R^(2d), CH₂NR^(2d)SO₂R^(2d), S(O)_(p)R^(2d),CH₂S(O)_(p)R^(2d), 5-6 membered carbocycle substituted with 0-2 R^(4c),—(CH₂)-5-6 membered carbocycle substituted with 0-2 R^(4c), 5-6 memberedheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), and —(CH₂)-5-6 membered heterocycle substituted with 0-2R^(4c) and consisting of: carbon atoms and 1-4 heteroatoms selected fromthe group consisting of N, O, and S(O)_(p) provided that S(O)_(p)R^(2d)forms other than S(O)₂H or S(O)H; and R^(4c) is selected from ═O, OH,OCH₃, OCH₂CH₃, OCH₂CH₂CH₃, OCH(CH₃)₂, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH═CH₂, CH≡CH, CH₂OH, CH₂OCH₃, CH₂OCH₂CH₃, CH₂OCH₂CH₂CH₃, CH₂OCH(CH₃)₂,F, Br, Cl, CF₃, NR²R^(2a), CH₂NR²R^(2a), C(O)R^(2c), CH₂C(O)R^(2c),NR²C(O)R^(2b), CH₂NR²C(O)R^(2b), C(O)NR²R^(2a), CH₂C(O)NR²R^(2a),SO₂NR²R^(2a), CH₂SO₂NR²R^(2a), NR²SO₂R^(5a), CH₂NR²SO₂R^(5a),S(O)_(p)R^(5a), and CH₂S(O)_(p)R^(5a).
 7. A compound according to claim6, wherein the compound is of

or a stereoisomer or pharmaceutically acceptable salt or solvate formthereof, wherein: P₄ is -G; M₄ is -A-B; A-B is selected from:

R^(2d), at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH(CH₃)₂, CH₂CH₂CH(CH₃)₂, CH₂CCH, CH₂CH₂OH, CH₂C(O)NH₂,cyclopropyl, CH₂-cyclopropyl, cyclobutyl, cyclopentyl, and thiazolyl;R^(2e), at each occurrence, is selected from CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH(CH₃)₂, CH₂CH₂CH(CH₃)₂, CH₂-cyclopropyl, cyclopropyl, andcyclopentyl; R^(4a) is substituted with 0-2 R^(4c) and selected frommorpholine, 1,1-dioxo-thiomorpholine, dihydropyridine, piperidine,piperazine, pyrrolidine, imidazole, imidazoline, imidazolidine,oxazoline, and thiazoline; and R^(4c) is selected from ═O, OH, OCH₃, andCH₃.
 8. A compound according to claim 1, wherein the compound isselected from the group: Examples 3-30, 32-33, 37-44, 61, 109-118,135-146, 148-151, 154-165, 168-192, 195-199, 204-205, 207-213, 215, 217,219-232, 235-237, 240-241, and, 244-255.
 9. A compound according toclaim 1, wherein the compound is of Formula IIIa, IIIb, or IIIc:

or a stereoisomer or pharmaceutically acceptable salt, solvate, orprodrug form thereof, wherein; ring M, including M₁, M₂, and, ifpresent, M₃, is phenyl or a 3-10 membered carbocyclic or 4-10 memberedheterocyclic ring consisting of: carbon atoms and 1-4 heteroatomsselected from O, S(O)_(p), N, and NZ²; ring M is substituted with 0-3R^(1a) and 0-2 carbonyl groups, and there are 0-3 ring double bonds; oneof P₄ and M₄ is -Z-A-B and the other -G₁-G; G is a group of Formula IIaor IIb:

in formula IIa, ring E is substituted with 1-2 R^(a), provided that atleast one R^(a) is ortho to the point of attachment of ring E; informula IIb, ring D is substituted with 1-2 R^(a), provided that atleast one R^(a) is ortho to the point of attachment of ring D; ring D,including the two atoms of Ring E to which it is attached, is a 5-6membered ring consisting of: carbon atoms and 0-2 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p); ring D is substitutedwith 0-2 R and there are 0-3 ring double bonds; E is selected fromphenyl, pyridyl, pyrimidyl, pyrazinyl, and pyridazinyl, and issubstituted with 0-2 R; alternatively, ring D is absent, and ring E isselected from phenyl, pyridyl, pyrimidyl, and thienyl, and ring E issubstituted with 0-2 R; alternatively, ring D is absent, ring E isselected from phenyl, pyridyl, and thienyl, and ring E is substitutedwith 0-2 R and a 5-6 membered heterocycle consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), wherein the 5-6 membered heterocycle is substituted with 0-2carbonyl and 1-2 R and there are 0-3 ring double bonds; R is selectedfrom H, C₁₋₄ alkyl, F, Cl, OH, OCH₃, OCH₂CH₃, OCH(CH₃)₂, CN, C(═NH)NH₂,C(═NH)NHOH, C(═NH)NHOCH₃, NH₂, NH(C₁₋₃ alkyl), N(C₁₋₃ alkyl)₂,C(═NH)NH₂, CH₂NH₂, CH₂NH(C₁₋₃ alkyl), CH₂N(C₁₋₃ alkyl)₂,(CR⁸R⁹)_(t)NR⁷R⁸, C(O)NR⁷R⁸, CH₂C(O)NR⁷R⁸, S(O)_(p)NR⁷R⁸,CH₂S(O)_(p)NR⁷R⁸, SO₂R³, and OCF₃; alternatively, when 2 R groups areattached to adjacent atoms, they combine to form methylenedioxy orethylenedioxy; R^(a) is (CR⁸R⁹)₀₋₁R^(b)(CR⁸R^(2b))₀₋₄R^(b)₀₋₁(CR⁸R⁹)₀₋₁R^(c); R^(b) is selected from O, C(O), C(O)NR³,C(O)N((CH₂)₂₋₃R³), S(O), S(O)₂, S(O)₂NR³, NR³, NR³C(O), and NR³S(O)₂;R^(c) is selected from H, OR³, NR³C(O)R³, C(O)R³, CO₂R³, C(O)NR³R^(3a),S(O)₂NR³R^(3a), —CN, C₃₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-12membered heterocycle substituted with 0-2 R⁴ and consisting of: carbonatoms and 1-4 heteroatoms selected from the group consisting of N, O,and S(O)_(p); R^(c) is selected from H, OR³, NR³C(O)R³, C(O)R³, CO₂R³,C(O)NR³R^(3a), S(O)₂NR³R^(3a), C₅₋₁₀ carbocycle substituted with 0-2 R⁴,and 5-10 membered heterocycle substituted with 0-2 R⁴ and consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p); provided that when the (CR⁸R^(2b))₀₋₄R^(b)₀₋₁(CR⁸R⁹)₀₋₁ portion of R^(a) is absent, then R^(c) is selected fromNR³C(O)R³, S(O)₂NR³R^(3a), C₅₋₁₀ carbocycle substituted with 0-2 R⁴, and5-10 membered heterocycle substituted with 0-2 R⁴ and consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p); further provided that when the R^(a) is C(O)—NR*R*and NR*R* is a heterocyclic ring, then the heterocyclic ring issubstituted with 1-2 R⁴; further provided that the (CR⁸R^(2b))₀₋₄R^(b)₀₋₁(CR⁸R⁹)₀₋₄R^(c) portion of R^(a) is other than(CR⁸R^(2b))₀₋₃-unsubstituted-phenyl or (CR⁸R⁹)₀₋₃-unsubstituted-phenyl;A is selected from: C₅₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-10membered heterocycle consisting of: carbon atoms and 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p) and substitutedwith 0-2 R⁴; B is selected from Y, X—Y, N(B¹)C(O)C(R³R^(3g))NB²B³,N(B¹)C(O)C(R³R^(3g))C(R³R^(3g))NB²B³,

provided that Z and B are attached to different atoms on A, the R^(4d)shown is other than OH, and that the A-X—N moiety forms other than aN—N—N group; B¹ is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, —(CH₂)₀₋₁—C₃₋₇carbocycle substituted with 0-2 R^(4b), and —(CH₂)₀₋₁-5-6 memberedheterocycle consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p) and substituted with 0-2R^(4b); B² is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, NR^(2d)R^(2d),CH₂—NR^(2d)R^(2d), CH₂CH₂—NR^(2d)R^(2d), C(O)R^(2e), C(O)NR^(2d)R^(2d),SO₂NR^(2d)R^(2d), and S(O)_(p)R^(5a); B³ is selected from H, C₁₋₆ alkylsubstituted with 0-1 R^(4c), —(CH₂)₀₋₁-3-6 membered carbocyclesubstituted with 0-1 R⁵, and a —(CH₂)₀₋₁-5-6 membered heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p) and substituted with 0-1 R⁵; B⁴ isselected from H, SO₂R^(3b), C(O)R^(3b), SO₂NR³R^(3b), C(O)NR³R^(3b),OR², and —CN; B is NR²R^(2f) or CR³R²R^(2f); ring Q is a 5-6 memberedring consisting of, in addition to the Q¹-CR⁴=Q² group shown, carbonatoms and 0-2 heteroatoms selected from N, O, and S(O)_(p), and the ringis substituted with an additional 0-2 R^(4d); Q¹ and Q² are each N;alternatively, Q¹ is CR³ and R^(4d) is NR²R^(2a) or NR^(3a)B⁴, providedthat when Q¹ is CR³, then this R³ group optionally forms a ring with theR² group of R^(4d), this ring is a 5-6 membered ring consisting of, inaddition to the C—C—N shown, carbon atoms and from 0-1 additionalheteroatoms selected from N, O, and S(O)_(p), and this ring issubstituted with 0-1 R⁵; Q⁴ is selected from C═O and SO₂; ring Q³ is a4-7 membered monocyclic or tricyclic ring consisting of, in addition tothe N-Q⁴ group shown, carbon atoms and 0-2 heteroatoms selected fromNR^(4c), O, S, S(O), and S(O)₂, wherein: 0-2 double bonds are presentwithin the ring and the ring is substituted with 0-2 R⁴; alternatively,ring Q³ is a 4-7 membered ring to which another ring is fused, wherein:the 4-7 membered ring consists of, in addition to the shown amide group,carbon atoms and 0-2 heteroatoms selected from NR^(4c), O, S, S(O), andS(O)₂ and 0-1 double bonds are present within the ring; the fusion ringis phenyl or a 5-6 membered heteroaromatic consisting of carbon atomsand 1-2 heteroatoms selected from NR^(4c), O, and S; ring Q³, whichincludes the 4-7 membered ring and the fusion ring, is substituted with0-3 R⁴; ring Q⁵ is a C₃₋₇ monocyclic carbocycle or 3-7 memberedmonocyclic heterocycle, wherein the carbocycle or heterocycle consistsof: carbon atoms and 0-2 heteroatoms selected from N, O, and S(O)_(p),the carbocycle or heterocycle further comprises 0-2 double bonds and 0-2carbonyl groups, and the carbocycle or heterocycle is substituted with0-2 R⁴; X is selected from —CR²R^(2a))₁₋₄—, —C(O)—, —C(═NR^(1c))—,—CR²(NR^(1b)R²)—, —C(O)CR²R^(2a)—, —CR²R^(2a)C(O), —C(O)NR²—, —NR²C(O)—,—C(O)NR²CR²R^(2a)—, —NR²C(O)CR²R^(2a)—, —CR²R^(2a)C(O)NR²—,—CR²R^(2a)NR²C(O)—, —NR²C(O)NR²—, —NR²—, —NR²CR²R^(2a)—, —CR²R^(2a)NR²—,—S(O)₂—, —NR²S(O)₂—, O, —CR²R^(2a)O—, and —OCR²R^(2a)—; Y is selectedfrom: CY¹Y²R^(4a), NR³R^(3a) and C(O)NR³R^(3a); Y¹ and Y² areindependently C₁₋₃ alkyl substituted with 0-2 R⁴; alternatively, Y isselected from one of the following carbocyclic and heterocycles that aresubstituted with 1 R^(4a) and 0-2 R⁴: cyclopropyl, cyclopentyl,cyclohexyl, phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl,furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl,isoxazolyl, isoxazolinyl, thiazolyl, isothiazolyl, pyrazolyl,imidazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl,1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl,1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl,1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, benzofuranyl,benzothiofuranyl, indolyl, benzimidazolyl, benzoxazolyl, benzthiazolyl,indazolyl, benzisoxazolyl, benzisothiazolyl, and isoindazolyl; Z isselected from a bond, CH₂, CH₂CH₂, CH₂O, OCH₂, C(O), NH, CH₂NH, NHCH₂,CH₂C(O), C(O)CH₂, C(O)NH, NHC(O), NHC(O)CH₂C(O)NH, S(O)₂, CH₂S(O)₂,S(O)₂(CH₂), SO₂NH, and NHSO₂, wherein the right side of Z is attached toring A, provided that Z does not form a N—S, NCH₂N, NCH₂O, or NCH₂S bondwith either group to which it is attached; Z² is selected from H, C₁₋₄alkyl, phenyl, benzyl, C(O)R^(3b), S(O)R^(3f), and S(O)₂R^(3f); R^(1a),at each occurrence, is selected from H, —(CH₂)_(r)—R^(1b),—(CH(CH₃))_(r)—R^(1b), —(C(CH₃)₂)_(r)—R^(1b), —O—(CR³R^(3a))_(r)—R^(1b),—NR²—(CR³R^(3a))_(r)—R^(1b), and —S—(CR³R^(3a))_(r)—R^(1b), providedthat R^(1a) forms other than an N-halo, N—S, O—O, or N—CN bond;alternatively, when two R^(1a) groups are attached to adjacent atoms,together with the atoms to which they are attached they form a 5-7membered ring consisting of: carbon atoms and 0-2 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), this ring beingsubstituted with 0-2 R^(4b) and 0-3 ring double bonds; R^(1b) isselected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, F, Cl, Br, I, —CN,—CHO, CF₃, OR², NR²R^(2a), C(O)R^(2b), CO₂R^(2b), OC(O)R², CO₂R^(2a),S(O)_(p)R², NR²(CH₂)_(r)OR², NR²C(O)R^(2b), NR²C(O)NHR², NR²C(O)₂R^(2a),OC(O)NR²R^(2a), C(O)NR²R^(2a), C(O)NR²(CH₂)_(r)OR², SO₂NR²R^(2a),NR²SO₂R², C₅₋₆ carbocycle substituted with 0-2 R^(4b), and 5-6 memberedheterocycle consisting of carbon atoms and from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-2 R^(4b), provided that R^(1b) forms other than an O—O, N-halo, N—S,or N—CN bond; R², at each occurrence, is selected from H, CF₃, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃,C(CH₃)₃, benzyl substituted with 0-2 R^(4b), C₅₋₆ carbocycle substitutedwith 0-2 R^(4b), a C₅₋₆ carbocyclic-CH₂-group substituted with 0-2R^(4b), and 5-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),and substituted with 0-2 R^(4b); R^(2a), at each occurrence, is selectedfrom H, CF₃, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, benzyl substituted with 0-2 R^(4b),C₅₋₆ carbocycle substituted with 0-2 R^(4b), and 5-6 memberedheterocycle consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-2 R^(4b); alternatively, NR²R^(2a) forms a 5 or 6 membered saturated,partially saturated or unsaturated ring substituted with 0-2 R^(4b) andconsisting of: 0-1 additional heteroatoms selected from the groupconsisting of N, O, and S(O)_(p); R^(2b), at each occurrence, isselected from CF₃, C₁₋₄ alkoxy, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, benzyl substitutedwith 0-2 R^(4b), C₅₋₆ carbocycle substituted with 0-2 R^(4b), and 5-6membered heterocycle consisting of: carbon atoms and 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p), andsubstituted with 0-2 R^(4b); R^(2c), at each occurrence, is selectedfrom CF₃, OH, C₁₋₄ alkoxy, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, benzyl substitutedwith 0-2 R^(4b), C₅₋₆ carbocycle substituted with 0-2 R^(4b), and 5-6membered heterocycle containing from 1-4 heteroatoms selected from thegroup consisting of N, O, and S(O)_(p), and substituted with 0-2 R^(4b);R^(2d), at each occurrence, is selected from H, R^(4c), C₁₋₄ alkylsubstituted with 0-2 R^(4c), —(CR³R^(3a))_(r)—C₃₋₆ carbocyclesubstituted with 0-2 R^(4c), and —(CR³R^(3a))_(r)-5-6 memberedheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), provided that R^(2d) forms other than a N-halo, N—C-halo,S(O)_(p)-halo, O-halo, N—S, S—N, S(O)_(p)—S(O)_(p), S—O, O—N, O—S, orO—O moiety; alternatively, NR^(2d)R^(2d) forms a 5 or 6 memberedsaturated, partially saturated or unsaturated ring substituted with 0-2R^(4b) and consisting of: 0-1 additional heteroatoms selected from thegroup consisting of N, O, and S(O)_(p); R^(2e), at each occurrence, isselected from H, R^(4c), C₁₋₄ alkyl substituted with 0-2 R^(4c),—(CR³R^(3a))_(r)—C₃₋₆ carbocycle substituted with 0-2 R^(4c), and—(CR³R^(3a))_(r)-5-6 membered heterocycle substituted with 0-2 R^(4c)and consisting of: carbon atoms and 1-4 heteroatoms selected from thegroup consisting of N, O, and S(O)_(p), provided that R^(2e) forms otherthan a C(O)-halo or C(O)—S(O)_(p) moiety; R^(2f), at each occurrence, isselected from H, CF₃, C₁₋₄ alkoxy, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, benzyl substitutedwith 0-1 R^(4b), C₅₋₆ carbocycle substituted with 0-2 R^(4b), and 5-6membered heterocycle containing from 1-4 heteroatoms selected from thegroup consisting of N, O, and S(O)_(p) and substituted with 0-2 R^(4b);alternatively, CR²R^(2f) forms a 5-6 membered ring consisting of: carbonatoms and 0-2 heteroatoms selected from N, O, and S(O)_(p), and thisring is substituted with 0-2 R^(4b); alternatively, NR²R^(2f) forms a5-6 membered ring consisting of: carbon atoms and 0-2 additionalheteroatoms selected from N, O, and S(O)_(p), and this ring issubstituted with 0-2 R^(4b); alternatively, when B⁵ is NR²R^(2f), B⁴ andR^(2f) combine to form a 5-6 membered ring consisting of: carbon atomsand 0-2 additional heteroatoms selected from N, O, and S(O)_(p), andthis ring is substituted with 0-2 R^(4b) and the R² group of NR²R², inaddition to the groups recited below, is selected from SO₂R^(3b) andC(O)R^(3b); R³, at each occurrence, is selected from H, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, benzyl, and phenyl; R^(3a), at each occurrence, isselected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzyl, and phenyl;alternatively, R³ and R^(3a), together with the nitrogen atom to whichthey are attached, combine to form a 5 or 6 membered saturated,partially unsaturated, or unsaturated ring consisting of: carbon atomsand the nitrogen atom to which R³ and R^(3a) are attached; R^(3b), ateach occurrence, is selected from H, CF₃, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, —(C₀₋₁ alkyl)-5-6 membered carbocycle substituted with 0-1R^(1a), and —(C₀₋₁ alkyl)-5-6 membered heterocycle substituted with 0-1R^(1a) and consisting of: carbon atoms and 1-4 heteroatoms selected fromthe group consisting of N, O, and S(O)_(p); R^(3c), at each occurrence,is selected from CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzyl, and phenyl;R^(3d), at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂-phenyl, CH₂CH₂-phenyl, and C(═O)R^(3c); R⁴, at eachoccurrence, is selected from ═O, OR², CH₂OR², (CH₂)₂OR², F, Cl, Br, I,C₁₋₄ alkyl, —CN, NO₂, NR²R^(2a), CH₂NR²R^(2a), (CH₂)₂NR²R^(2a),C(O)R^(2c), NR²C(O)R^(2b), C(O)NR²R^(2a), NR²C(O)NR²R^(2a),SO₂NR²R^(2a), NR²SO₂NR²R^(2a), S(O)_(p)R^(5a), NR²SO₂—C₁₋₄ alkyl,NR²SO₂R⁵, CF₃, CF₂CF₃, 5-6 membered carbocycle substituted with 0-1 R⁵,and a 5-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),and substituted with 0-1 R⁵; R^(4b), at each occurrence, is selectedfrom H, ═O, OR³, CH₂OR³, F, Cl, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, —CN, NO₂, NR³R^(3a),CH₂NR³R^(3a), C(O)R³, CH₂—C(O)R³, C(O)OR^(3c), CH₂C(O)OR^(3c),NR³C(O)R^(3a), CH₂NR³C(O)R^(3a), C(O)NR³R^(3a), CH₂C(O)NR³R^(3a),NR³C(O)NR³R^(3a), CH₂NR³C(O)NR³R^(3a), C(═NR³)NR³R^(3a),CH₂C(═NR³)NR³R^(3a), NR³C(═NR³)NR³R^(3a), CH₂NR³C(═NR³)NR³R^(3a),SO₂NR³R^(3a), CH₂SO₂NR³R^(3a), NR³SO₂NR³R^(3a), CH₂NR³SO₂NR³R^(3a),NR³SO₂—C₁₋₄ alkyl, CH₂NR³SO₂—C₁₋₄ alkyl, NR³SO₂CF₃, CH₂NR³SO₂CF₃,NR³SO₂-phenyl, CH₂NR³SO₂-phenyl, S(O)_(p)CF₃, CH₂S(O)_(p)CF₃,S(O)_(p)—C₁₋₄ alkyl, CH₂S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl,CH₂S(O)_(p)-phenyl, CF₃, and CH₂—CF₃; R^(4c), at each occurrence, isselected from ═O, (CR³R^(3a))_(r)OR², (CR³R^(3a))_(r)F,(CR³R^(3a))_(r)Br, (CR³R^(3a))_(r)Cl, (CR³R^(3a))_(r)CF₃, C₁₋₄ alkyl,C₂₋₃ alkenyl, C₂₋₃ alkynyl, (CR³R^(3a))_(r)CN, (CR³R^(3a))_(r)NO₂,(CR³R^(3a))_(r)NR²R^(2a), (CR³R^(3a))_(r)N(→O)R²R^(2a),(CR³R^(3a))_(r)C(O)R^(2c), (CR³R^(3a))_(r)NR²C(O)R^(2b),(CR³R^(3a))_(r)C(O)NR²R^(2a), (CR³R^(3a))_(r)NR²C(O)NR²R^(2a),(CR³R^(3a))_(r)SO₂NR²R^(2a), (CR³R^(3a))_(r)NR²SO₂NR²R^(2a),(CR³R^(3a))_(r)NR²SO₂R^(5a), (CR³R^(3a))_(r)C(O)NR²SO₂R^(5a),(CR³R^(3a))_(r)S(O)_(p)R^(5a), (CF₂)_(r)CF₃, (CR³R^(3a))_(r)C₃₋₁₀carbocycle substituted with 0-2 R^(4b), and (CR³R^(3a))_(r)5-10 memberedheterocycle consisting of carbon atoms and from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p) and substituted with 0-2R^(4b); R^(4d), at each occurrence, is selected from H, CH₂OR², OR²,C₁₋₄ alkyl, CH₂—CN, —CN, CH₂NO₂, NO₂, CH₂NR²R^(2a), NR²R^(2a),CH₂—C(O)R^(2c), C(O)R^(2c), NR²C(O)R^(2b), (CH₂)_(r)C(O)NR²R^(2a),NR²C(O)NR²R^(2a), (CH₂)_(r)SO₂NR²R^(2a), NR²SO₂NR²R^(2a), NR²SO₂R⁵,(CH₂)_(r)S(O)_(p)R^(5a), CH₂CF₃, CF₃, CH₂-5-6 membered carbocyclesubstituted with 0-1 R⁵, 5-6 membered carbocycle substituted with 0-1R⁵, a CH₂-5-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-1 R⁵, and a 5-6 membered heterocycle consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p) and substituted with 0-1 R⁵; R⁵, at each occurrence,is selected from H, ═O, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, OR³, CH₂OR³, F, Cl, —CN, NO₂,NR³R^(3a), CH₂NR³R^(3a), C(O)R³, CH₂C(O)R³, C(O)OR^(3c), CH₂C(O)OR^(3c),NR³C(O)R^(3a), C(O)NR³R^(3a), NR³C(O)NR³R^(3a), CH(═NOR^(3d)),C(═NR³)NR³R^(3a), NR³C(═NR³)NR³R^(3a), SO₂NR³R^(3a), NR³SO₂NR³R^(3a),NR³SO₂—C₁₋₄ alkyl, NR³SO₂CF₃, NR³SO₂-phenyl, S(O)_(p)CF₃, S(O)_(p)—C₁₋₄alkyl, S(O)_(p)-phenyl, CF₃, phenyl substituted with 0-2 R⁶, naphthylsubstituted with 0-2 R⁶, and benzyl substituted with 0-2 R⁶; R^(5a), ateach occurrence, is selected from CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, OR³, CH₂OR³,NR³R^(3a), CH₂NR³R^(3a), C(O)R³, CH₂C(O)R³, C(O)OR^(3c), CH₂C(O)OR^(3c),NR³C(O)R^(3a), CH₂NR³C(O)R^(3a), C(O)NR³R^(3a), CH₂C(O)NR³R^(3a), CF₃,CF₂CF₃, phenyl substituted with 0-2 R⁶, naphthyl substituted with 0-2R⁶, and benzyl substituted with 0-2 R⁶, provided that R^(5a) does notform a S—N or S(O)_(p)—C(O) bond; and R⁶, at each occurrence, isselected from H, OH, OR², F, Cl, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, CN, NO₂, NR²R^(2a),CH₂NR²R^(2a), C(O)R^(2b), CH₂C(O)R^(2b), NR²C(O)R^(2b),NR²C(O)NR²R^(2a), C(═NH)NH₂, NHC(═NH)NH₂, SO₂NR²R^(2a), NR²SO₂NR²R^(2a),and NR²SO₂C₁₋₄ alkyl.
 10. A compound according to claim 9, wherein thecompound is selected from:

G is substituted with 1 R^(a) and is selected from the following group,wherein R^(a) is attached adjacent to the point of attachment of G:

R^(a) is R^(b)(CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₁R^(c); R^(b) is selectedfrom C(O)NR³, S(O)₂NR³, NR³C(O), and NR³S(O)₂; R^(c) is selected from H,OR³, NR³C(O)R³, C(O)NR³R^(3a), C₅₋₁₀ carbocycle substituted with 0-2 R⁴,and 5-10 membered heterocycle substituted with 0-2 R⁴ and consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p); provided that when the (CR⁸R^(2b))₀₋₄R^(b)₀₋₁(CR⁸R⁹)₀₋₁ portion of R^(a) is absent, then R^(c) is selected fromNR³C(O)R³, C₅₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-10 memberedheterocycle substituted with 0-2 R⁴ and consisting of: carbon atoms and1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p); further provided that the (CR⁸R^(2b))₀₋₄R^(b)₀₋₁(CR⁸R⁹)₀₋₄R^(c) portion of R^(a) is other than(CR⁸R^(2b))₀₋₃-unsubstituted-phenyl or (CR⁸R⁹)₀₋₃-unsubstituted-phenyl;G₁ is absent or is selected from (CR³R^(3a))₁₋₃, CR³═CR³,(CR³R^(3a))_(u)C(O)(CR³R^(3a))_(w), (CR³R^(3a))_(u)O(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)C(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)C(O)(CR³R^(3a))_(w),(CR³R^(3a))_(u)NR^(3b)C(O)(CR³R^(3a))_(u)C(O)NR^(3b)(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(CR³R^(3a))_(w), (CR³R^(3a))_(u)S(O)(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(O)₂(CR³R^(3a))_(w),(CR³R^(3a))_(u)S(O)NR^(3b)(CR³R^(3a))_(w), (CR³R^(3a))_(u)NR^(3b)S(O)₂(CR³R^(3a))_(w), and(CR³R^(3a))_(u)S(O)₂NR^(3b)(CR³R^(3a))_(w), wherein u+w total 0, 1, or2, wherein the right side of G₁ is attached to ring G, provided that G₁does not form a N—S, NCH₂N, NCH₂O, or NCH₂S bond with either group towhich it is attached; A is selected from one of the followingcarbocyclic and heterocyclic groups which are substituted with 0-2 R⁴;cyclohexyl, phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl,furanyl, morpholinyl, thienyl, pyrrolyl, pyrrolidinyl, oxazolyl,isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl,1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl,1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl,1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl,1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, benzofuranyl,benzothiofuranyl, indolinyl, indolyl, benzimidazolyl, benzoxazolyl,benzthiazolyl, indazolyl, benzisoxazolyl, benzisothiazolyl, andisoindazolyl; B¹ is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,—(CH₂)₀₋₁—C₅₋₆ carbocycle substituted with 0-2 R^(4b), and —(CH₂)₀₋₁-5-6membered heterocycle consisting of: carbon atoms and 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p) and substitutedwith 0-2 R^(4b); B² is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, C(O)R^(2e), C(O)NR^(2d)R^(2d), SO₂NR^(2d)R^(2d), andS(O)_(p)R^(5a); B³ is selected from H, C₁₋₆ alkyl substituted with 0-1R^(4c), —(CH₂)₀₋₁-3-6 membered carbocycle substituted with 0-1 R⁵, and a—(CH₂)₀₋₁-5-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-1 R⁵; B⁴ is selected from H, SO₂R^(3b) and OR²; B⁵ isNR²R^(2f); ring Q is a 5-6 membered ring consisting of, in addition tothe N—CR⁴—N group shown, carbon atoms and 0-2 heteroatoms selected fromN, O, and S(O)_(p), and the ring is substituted with an additional 0-2R^(4d); Q⁴ is selected from C═O and SO₂; ring Q³ is a 5-7 membered ringconsisting of, in addition to the N-Q⁴ group shown, carbon atoms and 0-2heteroatoms selected from NR^(4c), O, S, S(O), and S(O)₂, wherein: 0-2double bonds are present within the ring and the ring is substitutedwith 0-2 R^(4a); alternatively, ring Q³ is a 5-7 membered ring to whichanother ring is fused, wherein: the 5-7 membered ring consists of, inaddition to the shown amide group, carbon atoms and 0-2 heteroatomsselected from NR^(4c), O, S, S(O), and S(O)₂, and 0-1 double bonds arepresent within the ring; the fusion ring is phenyl or a 5-6 memberedheteroaromatic consisting of carbon atoms and 1-2 heteroatoms selectedfrom NR^(4c), O, and S; ring Q³, which includes the 5-7 membered ringand the fusion ring, is substituted with 0-3 R^(4a); ring Q⁵, is a C₃₋₆monocyclic carbocycle or 5-6 membered monocyclic heterocycle, whereinthe carobocycle or heterocycle consists of carbon atoms and 0-2heteroatoms selected from N, O, and S(O)_(p), the carbocycle orheterocycle further comprises 0-1 double bonds and 0-1 carbonyl groups,and the carbocycle or heterocycle is substituted with 0-2 R⁴; X isselected from —(CR²R^(2a))₁₋₂—, —C(═NR^(1b))—, —C(O)—, —S(O)₂—,—NR²S(O)₂—, —NR²S(O)₂—, —NR²C(O)—, —C(O)NR²—, —NR²C(O)CR²R^(2a)—,—NR²C(O)NR²—, NR², —NR²CR²R^(2a)—, —CR²R^(2a)NR²—, O, —OCR²R^(2a)—, and—CR²R^(2a)O—; Y is selected from: CY¹Y²R^(4a), NR³R^(3a), andC(O)NR³R^(3a); Y¹ and Y² are independently C₁₋₂ alkyl substituted with0-2 R⁴; alternatively, Y is selected from one of the followingcarbocyclic and heterocycles that are substituted with 1 R^(4a) and 0-1R⁴: cyclopentyl, cyclohexyl, phenyl, piperidinyl, piperazinyl, pyridyl,pyrimidyl, furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl,oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl,oxadiazole, thiadiazole, triazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole,1,2,5-oxadiazole, 1,3,4-oxadiazole, 1,2,3-thiadiazole,1,2,4-thiadiazole, 1,2,5-thiadiazole, 1,3,4-thiadiazole, 1,2,3-triazole,1,2,4-triazole, 1,2,5-triazole, 1,3,4-triazole, benzofuran,benzothiofuran, indole, benzimidazole, benzimidazolone, benzoxazole,benzthiazole, indazole, benzisoxazole, benzisothiazole, and isoindazole;R^(1a) is selected from H, R^(1b), CH(CH₃)R^(1b), C(CH₃)₂R^(1b),CH₂R^(1b), and CH₂CH₂R^(1b), provided that R^(1a) forms other than anN-halo, N—S, or N—CN bond; alternatively, when two R^(1a) groups areattached to adjacent atoms, together with the atoms to which they areattached they form a 5-6 membered ring consisting of: carbon atoms and0-2 heteroatoms selected from the group consisting of N, O, andS(O)_(p), this ring being substituted with 0-2 R^(4b) and 0-3 ringdouble bonds; R^(1b) is selected from H, CH₃, CH₂CH₃, F, Cl, Br, —CN,—CHO, CF₃, OR², NR²R^(2a), C(O)R^(2b), CO₂R^(2b), OC(O)R², CO₂R^(2a),S(O)_(p)R², NR²(CH₂)_(r)OR², NR²C(O)R^(2b), C(O)NR²R^(2a), SO₂NR²R^(2a),NR²SO₂R², phenyl substituted with 0-2 R^(4b), and 5-6 membered aromaticheterocycle consisting of carbon atoms and from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-2 R^(4b), provided that R^(1b) forms other than an O—O, N-halo, N—S,or N—CN bond; R², at each occurrence, is selected from H, CF₃, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, phenyl substituted with 0-2 R^(4b), abenzyl substituted with 0-2 R^(4b), and a 5-6 membered aromaticheterocycle consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-2 R^(4b); R^(2a), at each occurrence, is selected from H, CF₃, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzyl substituted with 0-2 R^(4b), phenylsubstituted with 0-2 R^(4b), and 5-6 membered aromatic heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p), and substituted with 0-2 R^(4b);alternatively, NR²R^(2a) forms a 5 or 6 membered saturated, partiallysaturated or unsaturated ring substituted with 0-2 R^(4b) and consistingof: 0-1 additional heteroatoms selected from the group consisting of N,O, and S(O)_(p); R^(2b), at each occurrence, is selected from CF₃, C₁₋₄alkoxy, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzyl substituted with 0-2R^(4b), phenyl substituted with 0-2 R^(4b), and 5-6 membered aromaticheterocycle consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-2 R^(4b); R^(2c), at each occurrence, is selected from CF₃, OH, OCH₃,OCH₂CH₃, OCH₂CH₂CH₃, OCH(CH₃)₂, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzylsubstituted with 0-2 R^(4b), phenyl substituted with 0-2 R^(4b), and 5-6membered aromatic heterocycle containing from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-2 R^(4b); R^(2d), at each occurrence, is selected from H, R^(4c), C₁₋₄alkyl substituted with 0-2 R^(4c), C₃₋₆ carbocycle substituted with 0-2R^(4c), —(CR³R^(3a))—C₃₋₆ carbocycle substituted with 0-2 R^(4c), 5-6membered heterocycle substituted with 0-2 R^(4c) and consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p), and —(CR³R^(3a))-5-6 membered heterocyclesubstituted with 0-2 R^(4c) and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),provided that R^(2d) forms other than a N-halo, N—C-halo, S(O)_(p)-halo,O-halo, N—S, S—N, S(O)_(p)—S(O)_(p), S—O, O—N, O—S, or O—O moiety;R^(2e), at each occurrence, is selected from H, R^(4c), C₁₋₄ alkylsubstituted with 0-2 R^(4c), C₃₋₆ carbocycle substituted with 0-2R^(4c), —(CR³R^(3a))—C₃₋₆ carbocycle substituted with 0-2 R^(4c), 5-6membered heterocycle substituted with 0-2 R^(4c) and consisting of:carbon atoms and 1-4 heteroatoms selected from the group consisting ofN, O, and S(O)_(p), and —(CR³R^(3a))-5-6 membered heterocyclesubstituted with 0-2 R^(4c) and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),provided that R^(2e) forms other than a C(O)-halo or C(O)—S(O)_(p)moiety; R^(2f), at each occurrence, is selected from H, CF₃, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, OCH₃, and benzyl; alternatively, NR²R^(2f)forms a 5-6 membered ring consisting of: carbon atoms and 0-2 additionalheteroatoms selected from N, O, and S(O)_(p), and this ring issubstituted with 0-2 R^(4b); alternatively, B⁴ and R^(2f) combine toform a 5-6 membered ring consisting of: carbon atoms and 0-1 additionalheteroatoms selected from N, O, and S(O)_(p), and this ring issubstituted with 0-2 R^(4b) and the R² group of NR²R^(2f), in additionto the groups recited below, can be SO₂R^(3b); R^(3b), at eachoccurrence, is selected from H, CF₃, CH₃, CH₂CH₃, CH₂CH₂CH₃, andCH(CH₃)₂; R⁴, at each occurrence, is selected from H, ═O, CH₂OR²,(CH₂)₂OR², OR², F, Cl, Br, I, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, —CN, NO₂, NR²R^(2a),CH₂NR²R^(2a), (CH₂)₂NR²R^(2a), C(O)R^(2c), NR²C(O)R^(2b), C(O)NR²R^(2a),NR²C(O)NR²R^(2a), SO₂NR²R^(2a), CF₃, and CF₂CF₃; R^(4a) is selected from—(CR³R^(3g))_(r)-5-6 membered carbocycle substituted with 0-3 R^(4c),—(CR³R^(3g))_(r)-5-6 membered heterocycle substituted with 0-3 R^(4c)and consisting of: carbon atoms and 1-4 heteroatoms selected from thegroup consisting of N, O, and S(O)_(p), (CR³R^(3g))_(r)NR^(2d)R^(2d),(CR³R^(3g))_(r)N(→O)R^(2d)R^(2d), (CR³R^(3g))_(r)OR^(2d),(CR³R^(3g))_(r)—NR^(2d)C(O)R^(2e), (CR³R^(3g))_(r)—C(O)R^(2e),(CR³R^(3g))_(r)—OC(O)R^(2e), (CR³R^(3g))_(r)—C(O)NR^(2d)R^(2d),(CR³R^(3g))_(r)—C(O)OR^(2d), (CR³R^(3g))_(r)—NR^(2d)C(O)NR^(2d)R^(2d),(CR³R³⁹)_(r)—NR^(2d)C(O)OR^(2d), (CR³R^(3g))_(r)—SO₂NR^(2d)R^(2d),(CR³R^(3g))_(r)—NR^(2d)SO₂R^(2d), and (CR³R^(3g))_(r)—S(O)_(p)R^(2d),provided that S(O)_(p)R^(2d) forms other than S(O)₂H or S(O)H; R^(4b),at each occurrence, is selected from H, ═O, OR³, CH₂OR³, F, Cl, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, —CN, NO₂, NR³R^(3a), CH₂NR³R^(3a), C(O)R³,CH₂C(O)R³, C(O)OR^(3c), CH₂—C(O)OR^(3c), NR³C(O)R^(3a),CH₂NR³C(O)R^(3a), C(O)NR³R^(3a), CH₂—C(O)NR³R^(3a), SO₂NR³R^(3a),CH₂SO₂NR³R^(3a), NR³SO₂—C₁₋₄ alkyl, CH₂NR³SO₂—C₁₋₄ alkyl, NR³SO₂-phenyl,CH₂NR³SO₂-phenyl, S(O)_(p)CF₃, CH₂S(O)_(p)CF₃, S(O)_(p)—C₁₋₄ alkyl,CH₂S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl, CH₂S(O)_(p)-phenyl, and CF₃;R^(4c), at each occurrence, is selected from ═O, OR², (CR³R^(3a))OR², F,(CR³R^(3a))F, Br, (CR³R^(3a))Br, Cl, (CR³R^(3a))Cl, CF₃, (CR³R^(3a))CF₃,C₂₋₃ alkenyl, C₂₋₃ alkynyl, C₁₋₄ alkyl, —CN, (CR³R^(3a))CN, NO₂,(CR³R^(3a))NO₂, NR²R^(2a), (CR³R^(3a))NR²R^(2a), N(→O)R²R^(2a),(CR³R^(3a))N(→O)R²R^(2a), C(O)R^(2c), (CR³R^(3a))C(O)R^(2c),NR²C(O)R^(2b), (CR³R^(3a))NR²C(O)R^(2b), C(O)NR²R^(2a),(CR³R^(3a))C(O)NR²R^(2a), NR²C(O)NR²R^(2a), (CR³R^(3a))NR²C(O)NR²R^(2a),SO₂NR²R^(2a), (CR³R^(3a))SO₂NR²R^(2a), NR²SO₂NR²R^(2a),(CR³R^(3a))NR²SO₂NR²R^(2a), NR²SO₂R^(5a), (CR³R^(3a))NR²SO₂R^(5a),S(O)_(p)R^(5a), (CR³R^(3a))S(O)_(p)R^(5a), CF₃, CF₂CF₃, C₃₋₁₀ carbocyclesubstituted with 0-2 R^(4b), (CR³R^(3a))C₃₋₁₀ carbocycle substitutedwith 0-2 R^(4b), 5-10 membered heterocycle consisting of carbon atomsand from 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p) and substituted with 0-2 R^(4b), and (CR³R^(3a))-5-10 memberedheterocycle consisting of carbon atoms and from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p) and substituted with 0-2R^(4b); R^(4d), at each occurrence, is selected from H, CH₂OR², OR²,CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂,CH(CH₃)CH₂CH₃, C(CH₃)₃, —CN, NO₂, CH₂NR²R^(2a), NR²R^(2a), C(O)R^(2c),NR²C(O)R^(2b), C(O)NR²R^(2a), NR²C(O)NR²R^(2a), NR²SO₂R⁵, SO₂NR²R^(2a),6 membered carbocycle substituted with 0-1 R⁵, and a 5-6 memberedheterocycle consisting of: carbon atoms and 1-2 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p) and substituted with 0-1R⁵; R⁵, at each occurrence, is selected from H, ═O, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, OR³, CH₂OR³, F, Cl, —CN, NO₂, NR³R^(3a),CH₂NR³R^(3a), C(O)R³, CH₂C(O)R³, C(O)OR^(3c), CH₂C(O)OR^(3c),NR³C(O)R^(3a), C(O)NR³R^(3a), SO₂NR³R^(3a), NR³SO₂—C₁₋₄ alkyl,NR³SO₂CF₃, NR³SO₂-phenyl, S(O)_(p)CF₃, S(O)_(p)—C₁₋₄ alkyl,S(O)_(p)-phenyl, CF₃, phenyl substituted with 0-2 R⁶, naphthylsubstituted with 0-2 R⁶, and benzyl substituted with 0-2 R⁶; and R⁶, ateach occurrence, is selected from H, OH, OR², F, Cl, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, —CN, NO₂, NR²R^(2a), CH₂NR²R^(2a), C(O)R^(2b),CH₂C(O)R^(2b), NR²C(O)R^(2b), SO₂NR²R^(2a), and NR²SO₂C₁₋₄ alkyl.
 11. Acompound according to claim 10, wherein: G is substituted with 1 R^(a)wherein R^(a) is attached adjacent to the point of attachment of G:R^(a) is R^(b)(CR⁸R^(2b))₀₋₃R^(b) ₀₋₁R^(c); R^(b) is C(O)NR³; R^(c) isselected from H, OR³, C₅₋₁₀ carbocycle substituted with 0-2 R⁴, and 5-10membered heterocycle substituted with 0-2 R⁴ and consisting of: carbonatoms and 1-4 heteroatoms selected from the group consisting of N, O,and S(O)_(p); provided that when the (CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₁portion of R^(a) is absent, then R^(c) is selected from C₅₋₁₀ carbocyclesubstituted with 0-2 R⁴ and 5-11 membered heterocycle substituted with0-2 R⁴ and consisting of: carbon atoms and 1-4 heteroatoms selected fromthe group consisting of N, O, and S(O)_(p); further provided that the(CR⁸R^(2b))₀₋₄R^(b) ₀₋₁(CR⁸R⁹)₀₋₄R^(c) portion of R^(a) is other than(CR⁸R^(2b))₀₋₃-unsubstituted-phenyl or (CR⁸R⁹)₀₋₃-unsubstituted-phenyl;G₁ is absent or is selected from CH₂, CH₂CH₂, CH₂O, OCH₂, NH, CH₂NH,NHCH₂, CH₂C(O), C(O)CH₂, C(O)NH, NHC(O), CH₂S(O)₂, S(O)₂(CH₂), SO₂NH,and NHSO₂, wherein the right side of G₁ is attached to ring G, providedthat G₁ does not form a N—S, NCH₂N, NCH₂O, or NCH₂S bond with eithergroup to which it is attached; A is selected from cyclohexyl, indolinyl,piperidinyl, piperazinyl, phenyl, pyridyl, and pyrimidyl, and issubstituted with 0-2 R⁴; B is selected from Y,N(B¹)C(O)C(R³R^(3g))NB²B³,

provided that Z and B are attached to different atoms on A, the R^(4d)shown is other than OH, and that the A-X—N moiety forms other than aN—N—N group; B¹ is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, andCH(CH₃)₂; B² is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, and CH(CH₃)₂;B³ is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, C₂₋₅ alkyl substituted with 1R^(4c), —(CH₂)₀₋₁-3-6 membered carbocycle substituted with 0-1 R⁵, and a—(CH₂)₀₋₁-5-6 membered heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-1 R⁵; B⁴ is selected from H, SO₂R^(3b), and OR²; B⁵is NR²R^(2f); ring Q is a 5-6 membered ring consisting of, in additionto the N—CR^(4d)═N group shown, carbon atoms and 0-1 heteroatomsselected from N, O, and S(O)_(p), and the ring is substituted with anadditional 0-2 R^(4d); Q⁴ is selected from C═O and SO₂; ring Q³ is a 6-7membered ring consisting of, in addition to the N-Q⁴ group shown, carbonatoms and 0-1 heteroatoms selected from NR^(4c), O, S, S(O), and S(O)₂,wherein: 0-2 double bonds are present within the ring and the ring issubstituted with 0-2 R⁴; alternatively, ring Q³ is a 5-7 membered ringto which another ring is fused, wherein: the 5-7 membered ring consistsof, in addition to the shown amide group, carbon atoms and 0-1heteroatoms selected from NR^(4c), O, S, S(O), and S(O)₂, and 0-1 doublebonds are present within the ring; the fusion ring is phenyl; ring Q³,which includes the 5-7 membered ring and the fusion ring, is substitutedwith 0-2 R⁴; ring Q⁵ is substituted with 0-1 R⁴ and is selected fromcyclopropyl, cyclobutyl, cyclopentyl, cyclopentanonyl, cyclohexyl,cyclohexanonyl, pyrrolidinyl, pyrrolidinonyl, piperidinyl,piperidinonyl, tetrahydrofuranyl, and tetrahydropyranyl; X is selectedfrom CH₂, C(O), —S(O)₂—, —NHC(O)—, —C(O)NH—, —CH₂NH—, O, and —CH₂O—; Yis selected from N(CH₃)₂, C(O)(CH₃)₂, C(CH₃)₂R^(4a) andC(CH₂CH₃)₂R^(4a); altneratively, Y is selected from phenyl, pyridyl,pyrrolidino, N-pyrrolidino-carbonyl, morpholino, N-morpholino-carbonyl,1,2,3-triazolyl, imidazolyl, and benzimidazolyl, and is substituted with1 R^(4a) and 0-1 R⁴; R^(1a), at each occurrence, is selected from H,R^(1b), CH(CH₃)R^(1b), C(CH₃)₂R^(1b), and CH₂R^(1b), provided thatR^(1a) forms other than an N-halo, N—S, or N—CN bond; R^(1b) is selectedfrom CH₃, CH₂CH₃, F, Cl, Br, —CN, CF₃, OR², NR²R^(2a), C(O)R^(2b),CO₂R^(2b), CO₂R^(2a), S(O)_(p)R², C(O)NR²R^(2a), SO₂NR²R^(2a), NR²SO₂R²,and 5-6 membered aromatic heterocycle consisting of carbon atoms andfrom 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), and substituted with 0-2 R^(4b), provided that R^(1b) formsother than an O—O, N-halo, N—S, or N—CN bond; R², at each occurrence, isselected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, phenyl substitutedwith 0-1 R^(4b), benzyl substituted with 0-1 R^(4b), and 5-6 memberedaromatic heterocycle consisting of: carbon atoms and 1-4 heteroatomsselected from the group consisting of N, O, and S(O)_(p), andsubstituted with 0-1 R^(4b); R^(2a), at each occurrence, is selectedfrom H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzyl substituted with 0-1R^(4b), phenyl substituted with 0-1 R^(4b), and 5-6 membered aromaticheterocycle consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-1 R^(4b); alternatively, NR²R^(2a) forms a 5 or 6 membered saturated,partially saturated or unsaturated ring substituted with 0-1 R^(4b) andconsisting of: 0-1 additional heteroatoms selected from the groupconsisting of N, O, and S(O)_(p); R^(2b), at each occurrence, isselected from OCH₃, OCH₂CH₃, OCH₂CH₂CH₃, OCH(CH₃)₂, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, benzyl substituted with 0-1 R^(4b), phenylsubstituted with 0-1 R^(4b), and 5-6 membered aromatic heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p), and substituted with 0-1 R^(4b);R^(2c), at each occurrence, is selected from OH, OCH₃, OCH₂CH₃,OCH₂CH₂CH₃, OCH(CH₃)₂, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, benzylsubstituted with 0-1 R^(4b), phenyl substituted with 0-1 R^(4b), and 5-6membered aromatic heterocycle containing from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), and substituted with0-1 R^(4b); R^(2d), at each occurrence, is selected from H, R^(4c), C₁₋₄alkyl substituted with 0-2 R^(4c), C₃₋₆ carbocycle substituted with 0-2R^(4c), —(CH₂)—C₃₋₆ carbocycle substituted with 0-2 R^(4c), 5-6 memberedheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), and —(CH₂)-5-6 membered heterocycle substituted with 0-2R^(4c) and consisting of: carbon atoms and 1-4 heteroatoms selected fromthe group consisting of N, O, and S(O)_(p), provided that R^(2d) formsother than a N-halo, N—C-halo, S(O)_(p)-halo, O-halo, N—S, S—N,S(O)_(p)—S(O)_(p), S—O, O—N, O—S, or O—O moiety; R^(2e), at eachoccurrence, is selected from H, R^(4c), C₁₋₄ alkyl substituted with 0-2R^(4c), C₃₋₆ carbocycle substituted with 0-2 R^(4c), —(CH₂)—C₃₋₆carbocycle substituted with 0-2 R^(4c), 5-6 membered heterocyclesubstituted with 0-2 R^(4c) and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),and —(CH₂)-5-6 membered heterocycle and consisting of: carbon atoms and1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), provided that R^(2e) forms other than a C(O)-halo orC(O)—S(O)_(p) moiety; R^(2f) at each occurrence, is selected from H,CH₃, CH₂CH₃, OCH₃, and benzyl; alternatively, NR²R^(2f) forms a 5-6membered ring consisting of: carbon atoms and 0-1 additional heteroatomsselected from N, O, and S(O)_(p), and this ring is substituted with 0-1R^(4b); alternatively, B⁴ and R^(2f) combine to form a 5 membered ringconsisting of: carbon atoms and 0-1 additional heteroatoms selected fromN, O, and S(O)_(p), and this ring is substituted with 0-2 R^(4b) and theR² group of NR²R^(2f), in addition to the groups recited below, can beSO₂R^(3b); R^(3b), at each occurrence, is selected from H and CH₃; R⁴,at each occurrence, is selected from H, ═O, OH, OR², CH₂OR², (CH₂)₂OR²,F, Br, Cl, I, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃,CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃, C(CH₃)₃, NR²R^(2a), CH₂NR²R^(2a),(CH₂)₂NR²R^(2a), C(O)R^(2c), NR²C(O)R^(2b), C(O)NR²R^(2a), SO₂NR²R^(2a),CF₃, and CF₂CF₃; R^(4a) is selected from —(CR³R^(3g))_(r)-5-6 memberedcarbocycle substituted with 0-3 R^(4c), —(CR³R^(3g))_(r)-5-6 memberedheterocycle substituted with 0-3 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), (CR³R^(3g))_(r)NR^(2d)R^(2d),(CR³R^(3g))_(r)N(→O)R^(2d)R^(2d), (CR³R^(3g))_(r)OR^(2d),(CR³R^(3g))_(r)—C(O)NR^(2d)R^(2d), (CR³R^(3g))_(r)—NR^(2d)C(O)R^(2e),(CR³R^(3g))_(r)—C(O)R^(2e), (CR³R^(3g))_(r)—NR^(2d)C(O)NR^(2d)R^(2d),(CR³R^(3g))_(r)—NR^(2d)C(O)OR^(2d), (CR³R^(3g))_(r)—NR^(2d)SO₂R^(2d),and (CR³R^(3g))_(r)—S(O)_(p)R^(2d), provided that S(O)_(p)R^(2d) formsother than S(O)₂H or S(O)H; R^(4b), at each occurrence, is selected fromH, ═O, OR³, CH₂OR³, F, Cl, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, —CN, NO₂,NR³R^(3a), CH₂NR³R^(3a), C(O)R³, C(O)OR^(3c), NR³C(O)R^(3a),C(O)NR³R^(3a), SO₂NR³R^(3a), NR³SO₂—C₁₋₄ alkyl, NR³SO₂-phenyl,S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl, and CF₃; R^(4c), at eachoccurrence, is selected from ═O, OR², CH₂OR², F, Br, Cl, CF₃, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃,C(CH₃)₃, C₂₋₃ alkenyl, C₂₋₃ alkynyl, —CN, NO₂, NR²R^(2a), CH₂NR²R^(2a),N(→O)R²R^(2a), CH₂N(→O)R²R^(2a), C(O)R^(2c), CH₂C(O)R^(2c),NR²C(O)R^(2b), CH₂NR²C(O)R^(2b), C(O)NR²R^(2a), CH₂C(O)NR²R^(2a),SO₂NR²R^(2a), CH₂SO₂NR²R^(2a), NR²SO₂R^(5a), CH₂NR²SO₂R^(5a),S(O)_(p)R^(5a), CH₂S(O)_(p)R^(5a), CF₃, CF₂CF₃, C₃₋₆ carbocyclesubstituted with 0-2 R^(4b), (CH₂)C₃₋₆ carbocycle substituted with 0-2R^(4b), 5-6 membered heterocycle consisting of carbon atoms and from 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-2 R^(4b), and (CH₂)-5-6 membered heterocycleconsisting of carbon atoms and from 1-4 heteroatoms selected from thegroup consisting of N, O, and S(O)_(p) and substituted with 0-2 R^(4b);R^(4d), at each occurrence, is selected from H, CH₂OR², OR², CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃,C(CH₃)₃, CH₂NR²R^(2a), NR²R^(2a), C(O)R^(2c), NR²C(O)R^(2b),C(O)NR²R^(2a), SO₂NR²R^(2a), NR²SO₂R⁵, phenyl substituted with 0-1 R⁵,and a 5-6 membered heterocycle consisting of: carbon atoms and 1heteroatom selected from the group consisting of N, O, and S(O)_(p) andsubstituted with 0-1 R⁵; R⁵, at each occurrence, is selected from H, ═O,CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, OR³, CH₂OR³, F, Cl, —CN, NO₂,NR³R^(3a), CH₂NR³R^(3a), C(O)R³, C(O)OR^(3c), NR³C(O)R^(3a),C(O)NR³R^(3a), SO₂NR³R^(3a), NR³SO₂—C₁₋₄ alkyl, NR³SO₂-phenyl,S(O)_(p)—C₁₋₄ alkyl, S(O)_(p)-phenyl, CF₃, phenyl substituted with 0-2R⁶, naphthyl substituted with 0-2 R⁶, and benzyl substituted with 0-2R⁶; and R⁶, at each occurrence, is selected from H, OH, OR², F, Cl, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, —CN, NO₂, NR²R^(2a), CH₂NR²R^(2a),C(O)R^(2b), CH₂C(O)R^(2b), NR²C(O)R^(2b), and SO₂NR²R^(2a).
 12. Acompound according to claim 11, wherein G₁ is absent or is selected fromCH₂NH, NHCH₂, CH₂C(O), C(O)CH₂, C(O)NH, NHC(O), NHC(O)NH, CH₂S(O)₂,S(O)₂(CH₂), SO₂NH, and NHSO₂, wherein the right side of G₁ is attachedto ring G, provided that G₁ does not form a N—S, NCH₂N, NCH₂O, or NCH₂Sbond with either group to which it is attached; A is selected from thegroup: cyclohexyl, indolinyl, phenyl, 2-pyridyl, 3-pyridyl, 2-pyrimidyl,2-Cl-phenyl, 3-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 2-methylphenyl,2-aminophenyl, and 2-methoxyphenyl; B is selected from Y,N(B¹)C(O)C(R³R^(3g))NB²B³,

provided that Z and B are attached to different atoms on A and that theR^(4d) shown is other than OH; B¹ is selected from H, CH₃, CH₂CH₃, andCH₂CH₂CH₃; B² is selected from H, CH₃, and CH₂CH₃; B³ is selected fromCH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, C(CH₃)₃,CH(CH₃)CH₂CH(CH₃)₂, CH₂CH₂OH, CH(CH₃)CH₂OH, CH(phenyl)CH₂CH₃,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and CH₂-cyclopropyl;

is attached to a different atom on A than M and is selected from thegroup:

ring Q⁵ is selected from cyclopropyl, cyclobutyl, cyclopentyl,2-cyclopentanonyl, cyclohexyl, 2-cyclohexanonyl, pyrrolidinyl (attachedto A and R^(4a) at the 2-position), pyrrolidinyl (attached to A andR^(4a) at the 3-position), 2-pyrrolidinonyl (attached to A and R^(4a) atthe 3-position), piperidinyl (attached to A and R^(4a) at the4-position), 4-piperdinonyl (attached to A and R^(4a) at the3-position), tetrahydrofuranyl, and tetrahydropyranyl (attached to A andR^(4a) at the 4-position); Y is selected from N(CH₃)₂, C(O)(CH₃)₂,C(CH₃)₂R^(4a) and C(CH₂CH₃)₂R^(4a); alternatively, Y is selected fromphenyl, pyridyl, 1,2,3-triazolyl, imidazolyl, and benzimidazolyl, and issubstituted with 1 R^(4a); R^(1a), at each occurrence, is selected fromH, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH₂F, CH₂Cl, Br, CH₂Br, —CN, CH₂CN, CF₃,CH₂CF₃, OCH₃, CH₂OH, C(CH₃)₂OH, CH₂OCH₃, NH₂, CH₂NH₂, NHCH₃, CH₂NHCH₃,N(CH₃)₂, CH₂N(CH₃)₂, CO₂H, COCH₃, CO₂CH₃, CH₂CO₂CH₃, SCH₃, CH₂SCH₃,S(O)CH₃, CH₂S(O)CH₃, S(O)₂CH₃, CH₂S(O)₂CH₃, C(O)NH₂, CH₂C(O)NH₂, SO₂NH₂,CH₂SO₂NH₂, NHSO₂CH₃, CH₂NHSO₂CH₃, pyridin-2-yl, pyridin-3-yl,pyridin-4-yl, pyridin-2-yl-N-oxide, pyridin-3-yl-N-oxide,pyridin-4-yl-N-oxide, imidazol-1-yl, CH₂-imidazol-1-yl,4-methyl-oxazol-2-yl, 4-N,N-dimethylaminomethyl-oxazol-2-yl,1,2,3,4-tetrazol-1-yl, 1,2,3,4-tetrazol-5-yl, CH₂-1,2,3,4-tetrazol-1-yl,and CH₂-1,2,3,4-tetrazol-5-yl, provided that R^(1a) forms other than anN-halo, N—S, or N—CN bond; R², at each occurrence, is selected from H,CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, phenyl substituted with 0-1 R^(4b),benzyl substituted with 0-1 R^(4b), and 5 membered aromatic heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p), and substituted with 0-1 R^(4b);R^(2a), at each occurrence, is selected from H, CH₃, and CH₂CH₃;alternatively, NR²R^(2a) forms a 5 or 6 membered saturated, partiallysaturated or unsaturated ring substituted with 0-1 R^(4b) and consistingof: 0-1 additional heteroatoms selected from the group consisting of N,O, and S(O)_(p); R^(2b), at each occurrence, is selected from OCH₃,OCH₂CH₃, CH₃, and CH₂CH₃; R^(2c), at each occurrence, is selected fromOH, OCH₃, OCH₂CH₃, CH₃, and CH₂CH₃; R^(2d), at each occurrence, isselected from H, R^(4c), C₁₋₄ alkyl substituted with 0-2 R^(4c), C₃₋₆cycloalkyl substituted with 0-2 R^(4c), phenyl substituted with 0-2R^(4c), and 5-6 membered aromatic heterocycle substituted with 0-2R^(4c) and consisting of: carbon atoms and 1-4 heteroatoms selected fromthe group consisting of N, O, and S(O)_(p), provided that R^(2d) formsother than a N-halo, N—C-halo, S(O)_(p)-halo, O-halo, N—S, S—N,S(O)_(p)—S(O)_(p), S—O, O—N, O—S, or O—O moiety; R^(2e), at eachoccurrence, is selected from H, R^(4c), C₁₋₄ alkyl substituted with 0-2R^(4c), C₃₋₆ cycloalkyl substituted with 0-2 R^(4c), phenyl substitutedwith 0-2 R^(4c), and 5-6 membered aromatic heterocycle substituted with0-2 R^(4c) and consisting of: carbon atoms and 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p), provided that R^(2e)forms other than a C(O)-halo or C(O)—S(O)_(p) moiety; R^(2f), at eachoccurrence, is selected from H, CH₃, CH₂CH₃, and OCH₃; alternatively,NR²R^(2f) forms a ring selected from morpholine, piperazine, piperidine,and pyrrolidine; R⁴, at each occurrence, is selected from H, ═O, CH₃,CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, CH₂CH(CH₃)₂, CH(CH₃)CH₂CH₃,and C(CH₃)₃; R^(4a) is selected from —(CH₂)_(r)-5-6 membered carbocyclesubstituted with 0-3 R^(4c), —(CH₂)_(r)-5-6 membered heterocyclesubstituted with 0-3 R^(4c) and consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),(CH₂)_(r)NR^(2d)R^(2d), (CH₂)_(r)N(→O)R^(2d)R^(2d), (CH₂)_(r)OR^(2d),(CH₂)_(r)—C(O)NR^(2d)R^(2d), (CH₂)_(r)—NR^(2d)C(O)R^(2e),(CH₂)_(r)—C(O)R^(2e), (CH₂)_(r)—NR^(2d)C(O)NR^(2d)R^(2d),(CH₂)_(r)—NR^(2d)C(O)OR^(2d), (CH₂)_(r)—NR^(2d)SO₂R^(2d), and(CH₂)_(r)—S(O)_(p)R^(2d), provided that S(O)_(p)R^(2d) forms other thanS(O)₂H or S(O)H; R^(4b), at each occurrence, is selected from H, ═O,OR³, CH₂OR³, F, Cl, CH₃, CH₂CH₃, NR³R^(3a), CH₂NR³R^(3a), C(O)R³,C(O)OR^(3c), NR³C(O)R^(3a), C(O)NR³R^(3a), SO₂NR³R^(3a), NR³SO₂-phenyl,S(O)₂CH₃, S(O)₂-phenyl, and CF₃; R^(4c), at each occurrence, is selectedfrom ═O, OH, OCH₃, OCH₂CH₃, OCH₂CH₂CH₃, OCH(CH₃)₂, CH₃, CH₂CH₃,CH₂CH₂CH₃, CH(CH₃)₂, C₂₋₃ alkenyl, C₂₋₃ alkynyl, CH₂OH, CH₂OCH₃,CH₂OCH₂CH₃, CH₂OCH₂CH₂CH₃, CH₂OCH(CH₃)₂, F, Br, Cl, CF₃, NR²R^(2a),CH₂NR²R^(2a), N(→O)R²R^(2a), CH₂N(→O)R²R^(2a), C(O)R^(2c),CH₂C(O)R^(2c), NR²C(O)R^(2b), CH₂NR²C(O)R^(2b), C(O)NR²R^(2a),CH₂C(O)NR²R^(2a), SO₂NR²R^(2a), CH₂SO₂NR²R^(2a), NR²SO₂R^(5a)CH₂NR²SO₂R^(5a), S(O)_(p)R^(5a), CH₂S(O)_(p)R^(5a), CF₃, cyclopropylsubstituted with 0-1 R^(4b), cyclobutyl substituted with 0-1 R^(4b),cyclopentyl substituted with 0-1 R^(4b), phenyl substituted with 0-1R^(4b), —CH₂-cyclopropyl substituted with 0-1 R^(4b), —CH₂-cyclobutylsubstituted with 0-1 R^(4b), —CH₂-cyclopentyl substituted with 0-1R^(4b), benzyl substituted with 0-2 R^(4b), 5-6 membered aromaticheterocycle consisting of carbon atoms and from 1-4 heteroatoms selectedfrom the group consisting of N, O, and S(O)_(p) and substituted with 0-2R^(4b), and (CH₂)-5-6 membered aromatic heterocycle consisting of carbonatoms and from 1-4 heteroatoms selected from the group consisting of N,O, and S(O)_(p) and substituted with 0-2 R^(4b); R^(4d), at eachoccurrence, is selected from H, OCH₃, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,NR²R^(2a), NR²C(O)R^(2b), NR²SO₂R⁵, phenyl, 2-oxo-pyrrolidinyl, and2-oxo-piperidinyl; R⁵, at each occurrence, is selected from H, ═O, CH₃,CH₂CH₃, OR³, CH₂OR³, F, Cl, NR³R^(3a), CH₂NR³R^(3a), C(O)R³,C(O)OR^(3c), NR³C(O)R^(3a), C(O)NR³R^(3a), SO₂NR³R^(3a), NR³SO₂—C₁₋₄alkyl, NR³SO₂-phenyl, S(O)₂—CH₃, S(O)₂-phenyl, CF₃, phenyl substitutedwith 0-2 R⁶, naphthyl substituted with 0-2 R⁶, and benzyl substitutedwith 0-2 R⁶; and R⁶, at each occurrence, is selected from H, OH, OR², F,Cl, CH₃, CH₂CH₃, NR²R^(2a), CH₂NR²R^(2a), C(O)R^(2b), CH₂C(O)R^(2b),NR²C(O)R^(2b), and SO₂NR²R^(2a).
 13. A compound according to claim 12,wherein: A is selected from the group: indolinyl, phenyl, 2-pyridyl,2-pyrimidyl, and 2-F-phenyl, wherein B is substituted at the 4-positionof A, except when A is indolinyl, then B is substituted at the6-position of A; B is selected from:

R^(2d), at each occurrence, is selected from H, C₁₋₄ alkyl substitutedwith 0-1 R^(4c), C₃₋₆ cycloalkyl substituted with 0-2 R^(4c), phenylsubstituted with 0-2 R^(4c), and a 5-6 membered aromatic heterocycleconsisting of: carbon atoms and 1-4 heteroatoms selected from the groupconsisting of N, O, and S(O)_(p), provided that R^(2d) forms other thana N-halo, N—C-halo, S(O)_(p)-halo, O-halo, N—S, S—N, S(O)_(p)—S(O)_(p),S—O, O—N, O—S, or O—O moiety; R^(2e), at each occurrence, is selectedfrom H, C₁₋₄ alkyl substituted with 0-1 R^(4c), C₃₋₆ cycloalkylsubstituted with 0-2 R^(4c), phenyl, substituted with 0-2 R^(4c), and5-6 membered aromatic heterocycle consisting of: carbon atoms and 1-4heteroatoms selected from the group consisting of N, O, and S(O)_(p),provided that R^(2e) forms other than a C(O)-halo or C(O)—S(O)_(p)moiety; R^(4a) is selected from NR^(2d)R^(2d), CH₂NR^(2d)R^(2d),CH₂CH₂NR^(2d)R^(2d), N(→O)R^(2d)R^(2d), CH₂N(→O)R^(2d)R^(2d),CH₂OR^(2d), C(O)R^(2e), C(O)NR^(2d)R^(2d), CH₂C(O)NR^(2d)R^(2d),NR^(2d)C(O)R^(2e), CH₂NR^(2d)C(O)R^(2e), NR^(2d)C(O)NR^(2d)R^(2d),CH₂NR^(2d)C(O)NR^(2d)R^(2d), NR^(2d)C(O)OR^(2d), CH₂NR^(2d)C(O)OR^(2d),NR^(2d)SO₂R^(2d), CH₂NR^(2d)SO₂R^(2d), S(O)_(p)R^(2d),CH₂S(O)_(p)R^(2d), 5-6 membered carbocycle substituted with 0-2 R^(4c),—(CH₂)-5-6 membered carbocycle substituted with 0-2 R^(4c), 5-6 memberedheterocycle substituted with 0-2 R^(4c) and consisting of: carbon atomsand 1-4 heteroatoms selected from the group consisting of N, O, andS(O)_(p), and —(CH₂)-5-6 membered heterocycle substituted with 0-2R^(4c) and consisting of: carbon atoms and 1-4 heteroatoms selected fromthe group consisting of N, O, and S(O)_(p) provided that S(O)_(p)R^(2d)forms other than S(O)₂H or S(O)H; and R^(4c) is selected from ═O, OH,OCH₃, OCH₂CH₃, OCH₂CH₂CH₃, OCH(CH₃)₂, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂,CH═CH₂, CH≡CH, CH₂OH, CH₂OCH₃, CH₂OCH₂CH₃, CH₂OCH₂CH₂CH₃, CH₂OCH(CH₃)₂,F, Br, Cl, CF₃, NR²R^(2a), CH₂NR²R^(2a), C(O)R^(2c), CH₂C(O)R^(2c),NR²C(O)R^(2b), CH₂NR²C(O)R^(2b), C(O)NR²R^(2a), CH₂C(O)NR²R^(2a),SO₂NR²R^(2a), CH₂SO₂NR²R^(2a), NR²SO₂R^(5a), CH₂NR²SO₂R^(5a),S(O)_(p)R^(5a), and CH₂S(O)_(p)R^(5a).
 14. A compound according to claim13, wherein the compound is selected from:

P₄ is -G; A-B is selected from:

R^(2d), at each occurrence, is selected from H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH(CH₃)₂, CH₂CH₂CH(CH₃)₂, CH₂CCH, CH₂CH₂OH, CH₂C(O)NH₂,cyclopropyl, CH₂-cyclopropyl, cyclobutyl, cyclopentyl, and thiazolyl;R^(2e), at each occurrence, is selected from CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH(CH₃)₂, CH₂CH₂CH(CH₃)₂, CH₂-cyclopropyl, cyclopropyl, andcyclopentyl; R^(4a) is substituted with 0-2 R^(4c) and selected frommorpholine, 1,1-dioxo-thiomorpholine, dihydropyridine, piperidine,piperazine, pyrrolidine, imidazole, imidazoline, imidazolidine,oxazoline, and thiazoline; and R^(4c) is selected from ═O, OH, OCH₃, andCH₃.
 15. A compound according to claim 1, wherein the compound isselected from the group: Examples 62-102 and 105-106.
 16. Apharmaceutical composition, comprising: a pharmaceutically acceptablecarrier and a therapeutically effective amount of a compound of claim 1or a pharmaceutically acceptable salt form thereof.
 17. A method fortreating a thromboembolic disorder, comprising: administering to apatient in need thereof a therapeutically effective amount of a compoundof claim 1 or a pharmaceutically acceptable salt form thereof.
 18. Amethod according to claim 17, wherein the thromboembolic disorder isselected from the group consisting of arterial cardiovascularthromboembolic disorders, venous cardiovascular thromboembolicdisorders, and thromboembolic disorders in the chambers of the heart.19. A method according to claim 17, wherein the thromboembolic disorderis selected from unstable angina, an acute coronary syndrome, atrialfibrillation, first myocardial infarction, recurrent myocardialinfarction, ischemic sudden death, transient ischemic attack, stroke,atherosclerosis, peripheral occlusive arterial disease, venousthrombosis, deep vein thrombosis, thrombophlebitis, arterial embolism,coronary arterial thrombosis, cerebral arterial thrombosis, cerebralembolism, kidney embolism, pulmonary embolism, and thrombosis resultingfrom (a) prosthetic valves or other implants, (b) indwelling catheters,(c) stents, (d) cardiopulmonary bypass, (e) hemodialysis, or (f) otherprocedures in which blood is exposed to an artificial surface thatpromotes thrombosis.